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A. Aramini et al. / Tetrahedron 65 (2009) 2015–2021
phosphorous (1.5 mmol) was added and the mixture was heated to
120 ꢀC. The progress of the reaction was monitored by LC–MS or
TLC. After disappearance of the starting material, the reaction
mixture was cooled to room temperature, and Na2S2O3 saturated
solution (5 mL) was added. The resulting aqueous phase was
extracted with EtOAc (3ꢃ5 mL). To the combined organic layers,
saturated solution of NaHCO3 (10 mL) was added and desired
product was extracted. The aqueous phase was gently acidified to
pH¼2 and extracted with EtOAc (3ꢃ5 mL). The combined organic
layers were dried over Na2SO4 and evaporated under vacuum to
give the corresponding 2-arylpropionic acid.
(180 mg, 91%). Mp 37–41 ꢀC. 1H NMR (CDCl3)
d
7.25ꢁ7.10 (m, 4H),
3.7 (q, 1H, J¼7.0 Hz), 2.35 (s, 3H), 1.50 (d, 3H, J¼7.0 Hz). ESI-MS:
164 (MꢁH)ꢁ.
4.8.7. 2-(4-{[(Trifluoromethyl)sulfonyl]oxy}phenyl)propanoic
acid (4d)3,4
Following the general procedure D and starting from 2d
(160 mg, 0.54 mmol), 4d was obtained as a white solid (155 mg,
96%) and used without further purification.
4.8.8. 2-(4-Chlorophenyl)propanoic acid (4e)3,4
Following the general procedure D and starting from 2e
(180 mg, 1.0 mmol), 4e was obtained as a white solid after purifi-
cation by flash chromatography (CHCl3/MeOH/AcOH 85:15:0.2)
(165 mg, 90%).
4.8. General procedure (D) for preparation 2-arylpropionic
and arylacetic acid by hydroiodic acid 57% aqueous solution
(Table 4)
Cyanohydrin or
a
-hydroxyacid derivatives (1.0 mmol) were
4.8.9. 2-(3-Hydroxyphenyl)propanoic acid (4f)3,4
suspended in 57% aqueous hydriodic acid (2.0 mL), the mixture was
heated at 90 ꢀC and the reaction was monitored by LC–MS or TLC.
After disappearance of the starting material, the reaction mixture
was cooled to room temperature, and Na2S2O3 saturated solution
(5 mL) was added. The resulting aqueous phase was extracted with
EtOAc (3ꢃ5 mL). To the combined organic layers, saturated solution
of NaHCO3 (10 mL) was added and desired product was extracted.
The aqueous phase was gently acidified to pH¼2 and extracted with
EtOAc (3ꢃ5 mL). The combined organic layers were dried over
Na2SO4 and evaporated under vacuum to give the corresponding 2-
arylpropionic acid.
Following the general procedure D and starting from 2f (150 mg,
0.83 mmol), 4f was obtained as a glassy solid (130 mg, 95%) and
used without further purification. 1H NMR (CDCl3)
d 7.30–7.20 (m,
1H), 6.70–6.90 (m, 3H), 3.70 (q, 1H, J¼7.0 Hz), 1.40 (d, 3H, J¼7.0 Hz).
ESI-MS: 165 (MꢁH)ꢁ.
4.8.10. 2-(4-Aminophenyl)propanoic acid hydrochloride (4g)3,4
Following the general procedure D and starting from 2g
(150 mg, 0.58 mmol), 4g was obtained as a light brown solid for
precipitation of its hydrochloride salt after treatment of the organic
phase with HCl (1 M) (90 mg, 78%). 1H NMR (D2O)
d 7.62 (d, 2H,
J¼7.0 Hz), 7.48 (d, 2H, J¼7.0 Hz), 3.98 (q, 1H, J¼7.0 Hz), 1.50 (d, 3H,
4.8.1. 2-(4-iso-Butylphenyl)propanoic acid (4a)3,4,6
Following the general procedure D and starting from 3a
(200 mg, 0.90 mmol), 4a was obtained as a white solid (171 mg,
92%) and used without further purification. Mp 47–50 ꢀC. 1H NMR
J¼7.0 Hz). ESI-MS: 164 (MꢁH)þ, 166 (MþH)ꢁ.
Compound 4g was also prepared starting from 2-(4-nitro-
phenyl)-2-hydroxypropanenitrile (2h) (190 mg, 1.0 mmol) and
following the general procedure
D to obtain 2-(4-amino-
(DMSO-d6)
d
7.35–7.20 (m, 4H), 3.70 (q, 1H, J¼7.0 Hz), 2.55 (d, 2H,
phenyl)propanoic acid hydrochloride (4g) (140 mg, 70%).
J¼7.0 Hz), 1.80 (m, 1H), 1.45 (d, 3H, J¼7.0 Hz), 0.85 (d, 6H, J¼7.0 Hz).
ESI-MS: 205 (MꢁH)ꢁ.
4.8.11. Phenylacetic acid (4i)
Following the general procedure and starting from 2i (133 mg,
4.8.2. 2-(4-{[(Trifluoromethyl)sulfonyl]oxy}phenyl)propanoic
acid (4d)3,4
1.0 mmol), 4i was obtained as a colourless oil (130 mg, 95%). 1H
NMR (CDCl3)
d 10.75 (br s, 1H), 7.40–7.20 (m, 5H), 3.56 (s, 2H). LC–
Following the general procedure D and starting from 3d
(160 mg, 0.54 mmol), 4d was obtained as a white solid (155 mg,
MS: 135 (MꢁH)ꢁ.
96%). Mp 53–54 ꢀC. 1H NMR (CDCl3)
d
7.55 (d, 2H, J¼7 Hz), 7.35 (d,
References and notes
2H, J¼7 Hz), 3.95 (q, 1H, J¼7.0 Hz), 1.55 (d, 3H, J¼7.0 Hz). ESI-MS:
297 (MꢁH)ꢁ. Anal. Calcd for C10H9F3O5S: C, 40.27; H, 3.04; S 10.75.
Found: C, 40.88, H, 3.10, S 10.7.
1. Van Damme, J. The Cytokine Handbook; Academic: New York, NY, 1994; pp 185–205.
2. Petersen, F.; Flad, H. D.; Brandt, E. J. Immunol. 1994, 5, 2467–2478.
3. Allegretti, M.; Bertini, R.; Cesta, M. C.; Bizzarri, C.; Di Bitonto, R.; Di Cioccio, V.;
Galliera, E.; Berdini, V.; Topai, A.; Zampella, G.; Russo, V.; Di Bello, N.; Nano, G.;
Nicolini, L.; Locati, M.; Fantucci, P.; Florio, S.; Colotta, F. J. Med. Chem. 2005, 48,
4312–4331.
4. Aramini, A.; Moriconi, A.; Colagioia, S.; Locati, M.; Bertini, R.; Vigilante, P.;
Allegretti, M. J. Med. Chem. 2007, 50, 3984–4002.
5. (a) Smith, M. B.; March, J. Advanced Organic Chemistry; Wiley, Hoboken:
New Jersey, NJ, 2007; p 1867; (b) Seayad, A.; Jayasree, S.; Chaudhari, R. V. Org.
Lett. 1999, 1, 459–461.
4.8.3. 2-(4-Chlorophenyl)propanoic acid (4e)3,4
Following the general procedure D and starting from 3e
(150 mg, 0.75 mmol), 4e was obtained as a white solid (129 mg,
89%). Mp 57–62 ꢀC. 1H NMR (CDCl3)
d
7.35ꢁ7.20(m, 4H), 3.70 (q, 1H,
J¼7.0 Hz), 1.50 (d, 3H, J¼7.0 Hz). ESI-MS: 183/185 ([35/37Cl] MꢁH)ꢁ.
6. Nicholson, J. S.; Adams, S. S. U.S. Patent 3,228,831, 1966.
7. Komatsu, N.; Uda, M.; Suzuki, H.; Takahashi, T.; Domae, T.; Wada, M. Tetrahe-
dron Lett. 1997, 41, 7215–7218.
8. Nutaitis, C. F.; Bernardo, J. E. Synth. Commun. 1990, 4, 487–493.
9. (a) Sakai, T.; Miyata, K. Bull. Chem. Soc. Jpn. 1989, 62, 3537–3541; (b) Toudic, F.;
4.8.4. 2-(4-iso-Butylphenyl)propanoic acid (4a)3,4
Following the general procedure D and starting from 2a (200 mg,
0.98 mmol), 4a was obtained as a white solid (182 mg, 90%).
`
`
Ple, N.; Turck, A.; Queguiner, G. Tetrahedron 2002, 58, 283–293.
10. Kumar, D. J. S.; ManKit, M. H.; Toyokuni, T. Tetrahedron Lett. 2001, 42,
5601–5603.
4.8.5. 2-Phenylpropanoic acid (4b)3,4
Following the general procedure D and starting from 2b
(200 mg, 1.2 mmol), 4b was obtained as a colourless oil (157 mg,
88%) and used without further purification. 1H NMR (CDCl3)
11. Drug Enforcement Administration, Statistical Reports, 1989.
12. (a) Fieser, L.; Fieser, M. Reagents for Organic Synthesis; Wiley: New York, NY,
1967; Vol. 1, p 449; (b) Marvel, C. S.; Hager, F. D.; Caudle, E. C. Org. Synth.
Collect. 1941; Vol. 1, 224.
13. Windahl, K. L.; McTigue, M. J.; Pearson, J. R.; Pratt, S. J.; Rowe, J. E.; Sear, E. M.
Forensic Sci. Int. 1995, 76, 97–114.
14. Cantrell, T. S.; Boban, J.; Johnson, L.; Allen, A. C. Forensic Sci. Int. 1988, 39, 39–53.
15. Albouy, D.; Moghadam, E. G.; Vinatoru, M.; Koenig, M. J. Organomet. Chem. 1997,
529, 295–299.
16. Review: Olah, G. A.; Narang, S. C. Tetrahedron 1982, 38, 2225–2277.
17. Sukata, K. Bull. Chem. Soc. Jpn. 1987, 60, 3820–3822.
d
7.40ꢁ7.20 (m, 5H), 3.8 (q, 1H, J¼7.0 Hz), 1.50 (d, 3H, J¼7.0 Hz). ESI-
MS: 149 (MꢁH)ꢁ.
4.8.6. 2-(4-Methylphenyl)propanoic acid (4c)3,4
Following the general procedure
2c (200 mg, 1.2 mmol), 4c was obtained as
D
and starting from
white solid
a