- α-Methylation of Ketones with Methanol Catalyzed by Ni/SiO2-Al2O3
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α-Methylation of ketones with methanol catalyzed by a cheap and easy to handle Ni/SiO2-Al2O3 was explored. After optimization of the reaction between propiophenone and methanol, the desired product was obtained in 95 % isolated yield. A wide range of ketones was methylated under the optimized conditions (16 examples). This procedure was extended to a three-component cross-benzylation-methylation of acetophenone.
- Charvieux, Aubin,Duguet, Nicolas,Métay, Estelle
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supporting information
p. 3694 - 3698
(2019/06/13)
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- Ligand-Controlled Chemoselective C(acyl)-O Bond vs C(aryl)-C Bond Activation of Aromatic Esters in Nickel Catalyzed C(sp2)-C(sp3) Cross-Couplings
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A ligand-controlled and site-selective nickel catalyzed Suzuki-Miyaura cross-coupling reaction with aromatic esters and alkyl organoboron reagents as coupling partners was developed. This methodology provides a facile route for C(sp2)-C(sp3) bond formation in a straightforward fashion by successful suppression of the undesired β-hydride elimination process. By simply switching the phosphorus ligand, the ester substrates are converted into the alkylated arenes and ketone products, respectively. The utility of this newly developed protocol was demonstrated by its wide substrate scope, broad functional group tolerance and application in the synthesis of key intermediates for the synthesis of bioactive compounds. DFT studies on the oxidative addition step helped rationalizing this intriguing reaction chemoselectivity: whereas nickel complexes with bidentate ligands favor the C(aryl)-C bond cleavage in the oxidative addition step leading to the alkylated product via a decarbonylative process, nickel complexes with monodentate phosphorus ligands favor activation of the C(acyl)-O bond, which later generates the ketone product.
- Chatupheeraphat, Adisak,Liao, Hsuan-Hung,Srimontree, Watchara,Guo, Lin,Minenkov, Yury,Poater, Albert,Cavallo, Luigi,Rueping, Magnus
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supporting information
p. 3724 - 3735
(2018/03/21)
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- A Coupling Approach for the Generation of α,α-Bis(enolate) Equivalents: Regioselective Synthesis of gem-Difunctionalized Ketones
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Regioselective α,α-difunctionalization adjacent to a ketone is a significant synthetic challenge. Here, we present a solution to this problem through the transition-metal-free coupling of esters with geminal bis(boron) compounds. This forms an α,α-bis(enolate) equivalent which can be trapped with electrophiles including alkyl halides and fluorinating agents. This presents an efficient, convergent synthetic strategy for the synthesis of unsymmetrical blocked ketones.
- Iacono, Carmelo E.,Stephens, Thomas C.,Rajan, Teena S.,Pattison, Graham
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supporting information
p. 2036 - 2040
(2018/02/19)
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- METHOD OF PRODUCING 2'-TRIFLUOROMETHYL GROUP-SUBSTITUTED AROMATIC KETONE
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A method produces a 2′-trifluoromethyl-substituted aromatic ketone and includes reacting a 2-halogen-substituted benzotrifluoride compound with magnesium metal to convert the compound to a Grignard reagent; and reacting the Grignard reagent with an acid anhydride; and then hydrolyzing the resultant to produce a 2′-trifluoromethyl-substituted aromatic ketone. The method of producing a 2′-trifluoromethyl-substituted aromatic ketone enables 2′-trifluoromethyl-substituted aromatic ketone to be produced without using expensive raw materials by generating a Grignard reagent as an intermediate and reacting this Grignard reagent with an acid anhydride in an efficient productivity. The 2′-trifluoromethyl-substituted aromatic ketone that is produced by the method of producing a 2′-trifluoromethyl-substituted aromatic ketone can be used as fine chemicals, raw materials for pharmaceuticals and agrochemicals, raw materials for resins and plastics, electronics and information related materials, optical materials, and the like.
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Paragraph 0042; 0043; 0044; 0045; 0046; 0047; 0055
(2017/04/18)
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- Alcohol Oxidations Using Reduced Polyoxovanadates
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A full account of our recently communicated room temperature alcohol oxidation using reduced polyoxovanadates (r-POVs) is presented. Extensive optimizations revealed optimal conditions employing 0.02 equiv. of r-POV catalyst Cs5(V14As8O42Cl), 5 equiv. tert-butyl hydrogen peroxide (tBuOOH) as the terminal co-oxidant, in an acetone solvent for the quantitative oxidation of aryl-substituted secondary alcohols to their ketone products. The substrate scope tolerates most aryl substituted secondary alcohols in good to quantitative yields while alkyl secondary and primary activated alcohols were sluggish in comparison under similar conditions. Catalyst recyclability was successful on a 1.0?mmol scale of starting alcohol 1-phenylethanol. The oxidation was also successfully promoted by the VIV/VV mixed valent polyoxovanadate (POV) Cs11Na3Cl5(V15O36Cl). Finally, a third POV, Cs2.64(V5O9)(AsO4)2, was investigated for catalytic activity using our established reaction protocol, but proved ineffective as compared to the other two r-POV catalysts. This study expands the field of POM-mediated alcohol oxidations to include underexplored r-POV catalysts. While our catalysts do not supplant the best catalysts known for the transformation, their study may inform the development of other novel oxidative transformations mediated by r-POVs.
- Campbell, McKenzie L.,Sulejmanovic, Dino,Schiller, Jacqueline B.,Turner, Emily M.,Hwu, Shiou-Jyh,Whitehead, Daniel C.
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- Stereoselective amination of racemic sec-alcohols through sequential application of laccases and transaminases
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A one-pot/two-step bienzymatic asymmetric amination of secondary alcohols is disclosed. The approach is based on a sequential strategy involving the use of a laccase/TEMPO catalytic system for the oxidation of alcohols into ketone intermediates, and their following transformation into optically enriched amines by using transaminases. Individual optimizations of the oxidation and biotransamination reactions have been carried out, studying later their applicability in a concurrent process. Therefore, 17 racemic (hetero) aromatic sec-alcohols with different substitutions in the aromatic ring have been converted into enantioenriched amines with good to excellent selectivities (90-99% ee) and conversion values (67-99%). The scalability of the process was also demonstrated when two different amine donors were used in the transamination step, such as isopropylamine and cis-2-buten-1,4-diamine. Satisfyingly, both sacrificial amine donors can shift the equilibrium toward the amine formation, leading to the corresponding isolated enantioenriched amines with good to excellent results.
- Martínez-Montero, Lía,Gotor, Vicente,Gotor-Fernández, Vicente,Lavandera, Iván
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supporting information
p. 474 - 480
(2017/06/23)
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- Room-temperature catalytic oxidation of alcohols with the polyoxovanadate salt Cs5(V14As8O42Cl)
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While many known methods for oxidation mediated by polyoxometalates (POMs) employ environmentally friendly co-oxidants, they tend to employ large catalyst loadings (e.g. 40 mol%) and costly high reaction temperatures (~90-135 °C) that potentially contribute to the degradation of the catalyst and reduce their effectiveness. Herein, we present some initial results demonstrating a room temperature catalytic oxidation using the reduced salt-inclusion polyoxometalate, Cs5(V14As8O42Cl), that contains polyoxovanadate (POV) clusters as an efficient catalyst (e.g., 2 mol%) in the transformation of secondary alcohols to their corresponding ketones in very good to quantitative yields. Further, the catalyst can be suspended on celite and recycled.
- Campbell, McKenzie L.,Sulejmanovic, Dino,Schiller, Jacqueline B.,Turner, Emily M.,Hwu, Shiou-Jyh,Whitehead, Daniel C.
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p. 3208 - 3213
(2016/05/24)
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- Transition-Metal-Free Self-Hydrogen-Transferring Allylic Isomerization
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Phenanthroline and tert-butoxide have been established as powerful radical initiators in reactions such as the SRN1-type coupling reactions due to the cooperation of large heteroarenes and a special feature of tert-butoxide. The first phenanthroline-tert-butoxide-catalyzed transition-metal-free allylic isomerization is described. The resulting ketones are key intermediates for indenes. The control experiments rule out the base-promoted allylic anion pathway. The radical pathway is supported by experimental evidence that includes kinetic study, kinetic isotope effect, isotope-labeling experiments, trapping experiments, and EPR experiments.
- Zheng, Hong-Xing,Xiao, Zu-Feng,Yao, Chuan-Zhi,Li, Qiang-Qiang,Ning, Xiao-Shan,Kang, Yan-Biao,Tang, Yong
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supporting information
p. 6102 - 6105
(2016/01/09)
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- DMF as carbon source: Rh-catalyzed α-methylation of ketones
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An unprecedented Rh-catalyzed direct methylation of ketones with N,N-dimethylformamide (DMF) is disclosed. The reaction shows a broad substrate scope, tolerating both aryl and alkyl ketones with various substituents. Mechanistic studies suggest that DMF delivers a methylene fragment followed by a hydride in the methylation process.
- Li, Yang,Xue, Dong,Lu, Wei,Wang, Chao,Liu, Zhao-Tie,Xiao, Jianliang
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supporting information
p. 66 - 69
(2014/01/23)
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- Rhodium-catalysed isomerisation of allylic alcohols in water at ambient temperature
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An environmentally benign method for the transformation of allylic alcohols into carbonyl compounds is described. Using [Rh(COD(CH3CN) 2]BF4 (2) in combination with 1,3,5-triaza-7- phosphaadamantane (PTA, 1) as the catalytic system in water results in a very fast redox isomerisation of a variety of secondary allylic alcohols at ambient temperature. Also, some primary allylic alcohols can be isomerised into the corresponding aldehydes. The active complex, which in some cases can be used in catalyst loadings as low as 0.5 mol%, is formed in situ from commercially available reagents. Based on deuterium labelling studies, a tentative mechanism involving metal-enone intermediates is presented.
- Ahlsten, Nanna,Lundberg, Helena,Martin-Matute, Belen
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supporting information; experimental part
p. 1628 - 1633
(2010/12/19)
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- THERAPEUTIC DRUGS FOR POLLAKIURIA AND URINARY INCONTINENCE CONTAINING OPTICAL ACTIVE PROPIOPHENON AND ITS SALTS
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Disclosed herein is a therapeutic agent for urinary frequency and incontinence, comprising an optically active propiophenone derivative or a pharmaceutically acceptable salt thereof as an effective ingredient. The therapeutic agent for urinary frequency and incontinence is an oral formulation comprising (-) - (R) -2-methyl-3- (1-pyrrolidinyl) - 4 '-trif luoromethyl-propiophenone hydrochloride as an effective ingredient. Unlike conventional therapeutic agents for urinary frequency and incontinence, the derivative has good therapeutic effects on urinary frequency and incontinence and minimal side effects because it acts on the central nervous system and inhibits micturition hyperreflexia. Thus, the present therapeutic agent can replace conventional therapeutic agents for urinary frequency and incontinence.
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Page/Page column 16-17
(2010/11/24)
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- Hydroboration with pyridine borane at room temperature
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Treatment of pyridine borane (Py·BH3) with iodine, bromine, or strong acids affords activated Py·BH2X complexes that are capable of hydroborating alkenes at room temperature. Evidence is presented for an unusual hydroboration mechanism involving leaving group displacement. In contrast to THF·BH3, hydroboration with Py·BH2I selectively affords the monoadducts. The crude hydroboration products are converted into synthetically useful potassium alkyltrifluoroborate salts upon treatment with methanolic KHF2. Copyright
- Clay, Julia M.,Vedejs, Edwin
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p. 5766 - 5767
(2007/10/03)
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- Diminished reactivity of ortho-substituted phenacyl bromides toward nucleophilic displacement
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A systematic increase of substitution rates by tert-butylamine on α-bromopropiophenones is observed with meta or para substituents with increasing electron-withdrawing ability (k x 103 L M-1 min-1 = 12.7 (p-CH3), 15.7 (o-F), 20.5 (H), 20.0 (p-Cl), 23.6 (m-Cl), 27.3 (p-CF3)). Within an ortho-substituted series, the reactivities decrease (k x 103 L M-1 min-1 = 7.64 (o-OCH3), 5.31 (o-CH3), 2.85 (o-Cl), 2.40 (o-CF3)). Ortho-substitution results occur from rotational barrier effects and an Aδσ + Bδσ + repulsion. The major bonding contribution between reaction and α-substituent centers (A-B) is only the σ bond. When π bonding is allowed between A and B (meta/para-substitution), delocalization and stabilization of the reacting center occurs.
- Kalendra, Diane M.,Sickles, Barry R.
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p. 1594 - 1596
(2007/10/03)
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- Evidence that the availability of an allylic hydrogen governs the regioselectivity of the Wacker oxidation
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The allylic hydrogen is found to have a dramatic effect on the regioselectivity of the Wacker oxidation, leading to the postulation that an agostic hydrogen or enyl (σ + π) complex helps to stabilise the key intermediate.
- Gaunt,Yu,Spencer
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p. 1844 - 1845
(2007/10/03)
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- Unexpected reactions of (cyclooctatetraene) diiron hexacarbonyl with aryllithium reagents: Crystal structures of [(CO) 3Fe(1-4-η:5-7-η-C8H9)(CO) 2Fe(COC6H5)]
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The reaction of (cyclooctatetraene)diiron hexacarbonyl (1) with aryllithium reagents ArLi (Ar = C6H5, o-, m-, p-CH3C6H4, p-CH3OC6H4) in ether at low temperature afforded acylmetalate intermediates. Subsequent alkylation with Et3OBF4 in aqueous solution at 0°C gave the (8,8-dihydro-1-4-η:5-7-η-cyclooctatrienyl)tricarbonylirondicarbonyl(arylfonnacyl)iron complexes [(CO)3Fe(1-4-η:5-7-η-C8H9)(CO)2Fe(COAr)] (2a-e) (2a, Ar = C6H5; 2b, Ar = o-CH3C6H4; 2c, Ar = m-CH3C6H4; 2d, Ar = p-CH3C6H4; 2e, Ar = p-CH3OC6H4) and (1-4-η:5-8-η-cyclooctatetraene)tricarbonylirondicarbonyl[ethoxy(aryl)carbene]iron complexes [(CO)3Fe(1-4-η:5-8-η-C8H8)(CO)2FeC(OC2H5)Ar] (3a-e) (3a, Ar = C6H5; 3b, Ar = o-CH3C6H4; 3c, Ar = m-CH3C6H4; 3d, Ar = p-CH3C6H4; 3e, Ar = p-CH3OC6H4). The structures of 2a and 3a have been established by X-ray diffraction studies, which indicate that the Fe(CO)3 unit and the (CO)2Fe(COC6H5) moiety in 2a and the (CO)2FeC(OC2H5)H6H5 moiety in 3a are on opposite sides of the cyclooctatetraene ring.
- Yu, Yong,Sun, Jie,Chen, Jiabi
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- Synthesis and antifungal activity of new azole derivatives containing an N-acylmorpholine ring
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A series of azole derivatives carrying an N-acylmorpholine ring are described. The compounds were chemically designed to simulate the lanosterol D ring, taking advantage of the conformational preferences of 2-alkyl-1- acylmorpholines. Three structural variables, the nature of the N-benzoyl group, the phenyl substituents, and the degree of oxidation at carbon 2 of the morpholine, were optimized for maximum activity. Only the (5R,6R) isomers showed antifungal activity. Cyclic hemiacetal (-)-39a (UR-9746) and cyclic ether (-)-41 (UR-9751) were selected for further development. In vitro, (-)- 41 was clearly more active than (-)-39a and somewhat less active than the acyclic counterpart (-)-7. In vivo activity was assessed by a systemic (mouse) and a vaginal (rat) candidosis model. In the former, (-)-39a, (-)- 41, and (-)-7 at 1 mg/kg given 1, 4, and 24 h postinfection displayed 90- 100% protection from mortality on day 9. Compound (-)-39a was slightly more potent than (-)-41 and similar in potency to (-)-7. The three compounds were superior in potency to fluconazole and similar in potency to SCH-42427 in this test. In the vaginal model, (-)-39a and (-)-41 given daily during 3 days after infection at 0.5 mg/kg showed high levels of protection on days 10 and 15. At 0.25 mg/kg, (-)-39a was slightly more potent than SCH-42427 and (-)-7 and superior in potency to (-)-41 and fluconazole in this model. Preliminary 28-day toxicity tests at 100 mg/kg/day po in rats indicated no or very mild adverse effects for the two UR compounds.
- Bartroli,Turmo,Alguero,Boncompte,Vericat,Garcia-Rafanell,Forn
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p. 3918 - 3932
(2007/10/03)
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- Synthesis and activity of 2-methyl-3-aminopropiophenones as centrally acting muscle relaxants
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Some novel 2-methyl-3-aminopropiophenones were synthesized and their centrally acting muscle relaxant activities were,evaluated for an inhibitory effect on the flexor reflex in rats. The structure-activity relationships are discussed. In this series 2-methyl-3-pyrrolidino-1-(4-trifluoromethylphenyl)-propan-1-one (28) showed significant centrally acting muscle relaxant activity. In addition, the activities of each enantiomer (28-(S) and (R)) were studied along with their acute toxicities. Compound 28-(R) was found to exhibit more potent activity and weaker acute toxicity than 28-(S). Accordingly, compound 28-(R) (NK433) is under development as a novel centrally acting muscle relaxant.
- Shiozawa,Narita,Izumi,Kurashige,Sakitama,Ishikawa
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- Orally active azole derivatives
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The present invention relates to new orally active azole derivatives with antifungal activity of formula I STR1 wherein: X is CH or N; Ar represents phenyl substituted with halogen and/or trifluoromethyl; Z is --C(=O)-- or --SO2 --; R1 is CN, CO2 H, CO2 R7, CONR8 R9 or CH2 Y and then R3 is hydrogen, or R1 together with R3 forms a ring of formula I' STR2 wherein B is O, hydroxy or hydrogen; R4 is C1-4 alkyl; R5, R6, R8 and R9 are hydrogen or C1-4 alkyl; Y is --OH, --OR7, --OC(=O)R7, --NR8 R9, --NHC(=O)OR7 ; R7 is C1 -C4 -alkyl, phenyl-C1 -C4 -alkyl or optionally substituted phenyl; when Z is --C(=O)--, R2 is optionally susbtituted phenyl, or naphtyl; when Z is --SO2 --, R2 is C1-4 alkyl, phenyl-C1-4 -alkyl or optionally susbtituted phenyl.
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- Novel orally active antifungal agents
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The present invention relates to novel orally active antifungal agents of general formula Iwherein R1 represents hydrogen and R2 represents hydrogen or C1 4 alkyl, or R1 and R2 together represent a group -(CH2)-; p is 0 or 1, and the salts and solvates thereof.
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- AN EFFICIENT METHOD FOR THE SYNTHESIS OF 1-ARYLALKYNES
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1-Arylalkynes are prepared from propiophenones in good yield via the sequence a) 2 equiv PCl5/Δ b) DBN or Δ and c) Mg metal.
- Engler, Thomas A.,Combrink, Keith D.,Ray, James E.
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p. 1735 - 1744
(2007/10/02)
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- Therapeutically useful 1-phenyl-2-piperidinoalkanol derivatives
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Compounds of the formula: STR1 wherein R1 is hydrogen, halogen, trifluoromethyl, alkyl, hydroxyl, alkyoxy, benzyloxy, alkanoyloxy, or benzoyloxy, or when R2 is hydroxyl or methoxy in the 4-position and R3 is hydrogen, R1 may also represent hydroxymethyl carbamoyl or alkoxycarbonyl, R2 is hydrogen, halogen, alkyl, hydroxyl, or alkoxy, R3 is hydrogen or alkyl, R4 is alkyl (in which case the compounds are (±)-erythro) or when R3 represents hydrogen, R4 may also be hydrogen, and R5 is hydrogen, halogen, alkyl, alkoxy, or three methoxy groups in the 3-, 4- and 5-positions and pharmaceutically acceptable acid addition salts thereof, with the exclusion of compounds wherein: (a) one of R1 and R2 is in the 4-position and is hydroxyl, alkoxy or benzyloxy, the other is in the 3-position and is hydrogen, hydroxyl, alkoxy or benzyloxy, and R3 and R5 are hydrogen and wherein: (b) R1 is in the 4-position and is halogen, R4 is methyl and R2, R3 and R5 are hydrogen, are useful as medicaments.
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