148992-43-2

Basic information

• Product Name: DIFLUOROACETALDEHYDE ETHYL HEMIACETAL
• Synonyms: DIFLUOROACETALDEHYDE ETHYL HEMIACETAL;1-ETHOXY-2,2-DIFLUOROETHANOL;1-ethoxy-2,2-difluoroethan-1-ol;EOS-61532
• CAS NO: 148992-43-2
• Molecular Formula: C₄H₈F₂O₂
• Molecular Weight: 126.1
• Product Categories: Fluorinated Building Blocks;Fluorinating Reagents & Building Blocks for Fluorinated Biochemical Compounds;Synthetic Organic Chemistry
• Mol File: 148992-43-2.mol
• Article Data: 16

Chemical Properties

• Boiling Point: 85.1°C at 760 mmHg
• Flash Point: 46.2°C
• Appearance: /
• Density: 1.145g/cm³
• Vapor Pressure: 44.9mmHg at 25°C
• Refractive Index: 1.3660-1.3720
• Storage Temp.: Refrigerator
• PKA: 11.11±0.20(Predicted)
• CAS DataBase Reference: DIFLUOROACETALDEHYDE ETHYL HEMIACETAL(CAS DataBase Reference)
• NIST Chemistry Reference: DIFLUOROACETALDEHYDE ETHYL HEMIACETAL(148992-43-2)
• EPA Substance Registry System: DIFLUOROACETALDEHYDE ETHYL HEMIACETAL(148992-43-2)

Safety Data

• Statements: 10
• Safety Statements: 16
• RIDADR: 3271
• HazardClass: 3
• PackingGroup: III
• Hazardous Substances Data: 148992-43-2(Hazardous Substances Data)

Usage

General Description

Difluoroacetaldehyde ethyl hemiacetal is a chemical compound that is used as an intermediate in the production of pharmaceuticals and other organic compounds. It is a derivative of acetaldehyde, and it is characterized by its two fluorine atoms. DIFLUOROACETALDEHYDE ETHYL HEMIACETAL is known for its use as a building block in organic synthesis, and it is also used in research and development activities for creating new chemicals or pharmaceuticals. Difluoroacetaldehyde ethyl hemiacetal is a colorless liquid with a strong, pungent odor, and it is primarily used in a laboratory setting for its reactivity and ability to undergo various chemical reactions.

InChI:InChI=1/C4H8F2O2/c1-2-8-4(7)3(5)6/h3-4,7H,2H2,1H3

Synthetic route

ethyl difluoroacetate (454-31-9) → 1-ethoxy-2,2-difluoroethanol (148992-43-2)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran; diethyl ether at -78℃; for 2.75h;	100%
With lithium aluminium tetrahydride In tetrahydrofuran; diethyl ether at -78℃; for 3h;	60%
With lithium aluminium tetrahydride In tetrahydrofuran; diethyl ether at -78℃; for 3h; Reagent/catalyst; Solvent;	60%

ethanol (64-17-5) + ethyl difluoroacetate (454-31-9) → 1-ethoxy-2,2-difluoroethanol (148992-43-2)

Conditions	Yield
With lithium aluminium tetrahydride 1.) Et2O, THF, -78 deg C, 3 h, 2.) Et2O, THF, rt, 2 h;

ethyl difluoroacetate (454-31-9) → difluoroethanol (359-13-7) + 1-ethoxy-2,2-difluoroethanol (148992-43-2)

Conditions	Yield
With sodium tetrahydroborate; cerium(III) chloride In methanol; water at -15℃; for 1h; Title compound not separated from byproducts;
With ruthenium(bis[2‐(ethylsulfanyl)ethyl]amine)(dichloro)(triphenylphosphine); hydrogen; sodium ethanolate In ethanol at 25℃; under 22502.3 Torr; for 4h; Reagent/catalyst; Solvent; Temperature; Pressure;

difluoroacetic acid methyl ester (433-53-4) + acetic acid (64-19-7) → difluoroacetaldehyde methyl hemiacetal (129660-32-8) + C4H6F4O2 + C6H10F4O3 + 1-ethoxy-2,2-difluoroethanol (148992-43-2)

Conditions	Yield
Stage #1: difluoroacetic acid methyl ester With [carbonylchlorohydrido{bis[2-(diphenylphosphinomethyl)ethyl]amino}ethylamino] ruthenium(II); hydrogen; sodium methylate In methanol at 15℃; under 7500.75 Torr; for 8h; Large scale; Stage #2: acetic acid In methanol at 66℃; under 15.7516 Torr; Reagent/catalyst; Solvent; Pressure; Temperature; Large scale;

ethyl difluoroacetate (454-31-9) → difluoroethanol (359-13-7) + difluoroacetaldehyde methyl hemiacetal (129660-32-8) + 1-ethoxy-2,2-difluoroethanol (148992-43-2)

Conditions	Yield
With [carbonylchlorohydrido{bis[2-(diphenylphosphinomethyl)ethyl]amino}ethylamino] ruthenium(II); hydrogen; sodium methylate In methanol at 15℃; under 7500.75 Torr; for 8.16667h; Pressure;

para-xylene (106-42-3) + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → 1,1-difluoro-2,2-bis(2',5'-dimethylphenyl)ethane (1314534-86-5)

Conditions	Yield
With boron trifluoride monohydrate In water at 0℃; for 0.5h; Friedel Crafts hydroxyalkylation;	98%

2-nitropropane (79-46-9) + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → 1,1-difluoro-3-methyl-3-nitro-2-butanol

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran	96%
With potassium carbonate In tetrahydrofuran Ambient temperature;	82%

3-(tertbutyldimethylsiloxyl)propylamine (115306-75-7) + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → (E)-N-(3-((tert-butyldimethylsilyl)oxy)propyl)-2,2-difluoroethan-1-imine

Conditions	Yield
In benzene for 18h; Dean-Stark; Reflux;	94%

Glycine tert-butyl ester (6456-74-2) + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → tert-butyl (E)-2-((2,2-difluoroethylidene)amino)acetate

Conditions	Yield
In benzene for 18h; Dean-Stark; Reflux;	93%

p-nitrophenoxyamine (33543-55-4) + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → C8H6F2N2O3

Conditions	Yield
at 50℃; for 24h; Sealed tube; Acidic conditions;	93%

nitroacetic acid ethyl ester (626-35-7) + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → ethyl 4,4-difluoro-3-hydroxy-2-nitro-2-butanoate

Conditions	Yield
With potassium carbonate In tetrahydrofuran Ambient temperature;	92%
With 2,8,9-(i-Pr)3-2,5,8,9-tetraza-1-phosphabicyclo[3,3,3]undecen In tetrahydrofuran

4-methoxy-aniline (104-94-9) + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → N-(2,2-difluoroethylidene)-4-methoxyaniline

Conditions	Yield
In toluene at 100℃; for 3h;	91%

methyl 2-acetylamino-2-(dimethoxyphosphinyl)acetate (89524-99-2) + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → (Z)-2-Acetylamino-4,4-difluoro-but-2-enoic acid methyl ester

Conditions	Yield
With potassium tert-butylate In dichloromethane	91%

methyl 4-nitrobutyrate (13013-02-0) + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → methyl 6,6-difluoro-5-hydroxy-4-nitrohexanoate

Conditions	Yield
With potassium carbonate In tetrahydrofuran Ambient temperature;	90%

para-difluorobenzene (540-36-3) + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → 1,1-difluoro-2,2-bis(2',5'-difluorophenyl)ethane (1314534-92-3)

Conditions	Yield
With boron trifluoride monohydrate In water at 20℃; for 5h; Friedel Crafts hydroxyalkylation;	90%

O-(2-nitrophenyl)hydroxylamine (38100-30-0) + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → C8H6F2N2O3

Conditions	Yield
at 50℃; for 24h; Sealed tube; Acidic conditions;	90%

1-(benzo[d][1,3]dioxol-5-yl)allyl acetate (34627-78-6) + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → (2S,3R)-3-(benzo[d][1,3]dioxol-5-yl)-1,1-difluoropent-4-en-2-ol

Conditions	Yield
With C49H36Cl2IrN2O6P2; potassium carbonate In tetrahydrofuran; ethanol; isopropyl alcohol at 100℃; for 24h; Inert atmosphere; Sealed tube; Molecular sieve; enantioselective reaction;	89%

1-ethoxy-2,2-difluoroethanol (148992-43-2) + O-(4-cyanophenyl)hydroxylamine (94831-79-5) → C9H6F2N2O

Conditions	Yield
at 50℃; for 24h; Sealed tube; Acidic conditions;	89%

N-(benzyloxycarbonyl)phosphonoglycine trimethyl ester (100945-15-1) + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → N-benzyloxycarbonyl-2-amino-4,4-difluoro-2-butenoic acid methyl ester

Conditions	Yield
Stage #1: N-(benzyloxycarbonyl)phosphonoglycine trimethyl ester With potassium tert-butylate In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: 1-ethoxy-2,2-difluoroethanol In tetrahydrofuran at 20℃; for 18h; Inert atmosphere;	87%

(R)-1-phenyl-ethyl-amine (3886-69-9) + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → (αR)-N-(2,2-difluoroethylidene)(α-methylbenzyl)amine

Conditions	Yield
In toluene at 100℃; for 3h;	86%

1-trifluoromethoxybenzene (456-55-3) + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → 1,1-difluoro-2,2-bis[p-(trifluoromethoxy)benzene]ethane (1314534-88-7)

Conditions	Yield
With boron trifluoride monohydrate In water at 0℃; for 1h; Friedel Crafts hydroxyalkylation;	86%

1-(quinolin-4-yl)allyl acetate + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → (2S,3R)-1,1-difluoro-3-(quinolin-4-yl)pent-4-en-2-ol

Conditions	Yield
With C49H36Cl2IrN2O6P2; potassium carbonate In tetrahydrofuran; ethanol; isopropyl alcohol at 100℃; for 24h; Inert atmosphere; Sealed tube; Molecular sieve; enantioselective reaction;	86%

4-chlorobenzylamine (104-86-9) + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → C9H8ClF2N (906559-43-1)

Conditions	Yield
In toluene at 0 - 100℃; for 2h;	85%

4'-Methoxy-acetophenon-cyclohexylimin (41801-73-4) + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → 4,4-difluoro-3-hydroxy-1-(4-methoxyphenyl)-1-butanone

Conditions	Yield
In hexane Heating;	84%

N-benzyl hydroxylalmine (622-30-0) + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → N-benzyl C-(difluoromethyl)nitrone

Conditions	Yield
With toluene-4-sulfonic acid In toluene for 0.1h; Dean-Stark; Reflux;	84%
With toluene-4-sulfonic acid In toluene for 0.5h; Reflux; Dean-Stark;

1-acetoxy-1-(4-bromophenyl)-2-propylene (1337953-40-8) + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → (2S,3R)-3-(4-bromophenyl)-1,1-difluoropent-4-en-2-ol

Conditions	Yield
With C49H36Cl2IrN2O6P2; potassium carbonate In tetrahydrofuran; ethanol; isopropyl alcohol at 100℃; for 24h; Inert atmosphere; Sealed tube; Molecular sieve; enantioselective reaction;	84%

1-Nitropropane (108-03-2) + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → 1,1-difluoro-3-nitro-2-pentanol

Conditions	Yield
With 2,8,9-(i-Pr)3-2,5,8,9-tetraza-1-phosphabicyclo[3.3.3]undecen In tetrahydrofuran	83%
With potassium carbonate In tetrahydrofuran Ambient temperature;	68%

ethyl 3-nitropropanoate (3590-37-2) + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → ethyl 5,5-difluoro-4-hydroxy-3-nitropentanoate

Conditions	Yield
With potassium carbonate In tetrahydrofuran Ambient temperature;	82%

1-ethoxy-2,2-difluoroethanol (148992-43-2) + 3-acetoxy-3-(4-(trifluoromethyl)phenyl)-1-propene (169172-22-9) → (2S,3R)-1,1-difluoro-3-(4-(trifluoromethyl)phenyl)pent-4-en-2-ol

Conditions	Yield
With C49H36Cl2IrN2O6P2; potassium carbonate In tetrahydrofuran; ethanol; isopropyl alcohol at 100℃; for 24h; Inert atmosphere; Sealed tube; Molecular sieve; enantioselective reaction;	82%

1'-acetoxyestragole (61691-82-5) + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → (2S,3R)-1,1-difluoro-3-(4-methoxyphenyl)pent-4-en-2-ol

Conditions	Yield
With C49H36Cl2IrN2O6P2; potassium carbonate In tetrahydrofuran; ethanol; isopropyl alcohol at 100℃; for 24h; Inert atmosphere; Sealed tube; Molecular sieve; enantioselective reaction;	82%

N-((1S)-1-phenylethyl)hydroxylamine (53933-47-4) + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → N-(S)-(α-methylbenzyl)-C-(difluoromethyl)nitrone

Conditions	Yield
With toluene-4-sulfonic acid In toluene for 0.5h; Reflux; Dean-Stark;	80%

1-phenyl-2-propenyl acetate (7217-71-2) + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → (2S,3R)-1,1-difluoro-3-phenylpent-4-en-2-ol

Conditions	Yield
With C49H36Cl2IrN2O6P2; potassium carbonate In tetrahydrofuran; ethanol; isopropyl alcohol at 100℃; for 24h; Inert atmosphere; Sealed tube; Molecular sieve; enantioselective reaction;	80%

nitromethane (75-52-5) + 1-ethoxy-2,2-difluoroethanol (148992-43-2) → 1,1-difluoro-3-nitro-2-propanol

Conditions	Yield
With 2,8,9-(i-Pr)3-2,5,8,9-tetraza-1-phosphabicyclo[3,3,3]undecen In tetrahydrofuran	79%
With potassium carbonate In tetrahydrofuran for 3h; Ambient temperature;	65%
With sodium carbonate
With sodium carbonate at 20 - 60℃;
With sodium carbonate at 20 - 60℃;

1-ethoxy-2,2-difluoroethanol (148992-43-2) + benzylamine (100-46-9) → N-(2,2-difluoroethylidene)benzylamine (148628-63-1)

Conditions	Yield
In toluene at 100℃; for 1h;	78%
In toluene Reflux;
With toluene-4-sulfonic acid In toluene Reflux; Dean-Stark;

Upstream product

• 64-17-5 ethanol 
• 454-31-9 ethyl difluoroacetate 
• 433-53-4 difluoroacetic acid methyl ester 
• 64-19-7 acetic acid 

Downstream Products

• 363190-30-1 2-[2-(4-tert-butylcarbamoyl-4-cyclohexyl-piperidin-1-yl)-1-(4-fluoro-benzyl)-2-oxo-ethylcarbamoyl]-4-(2,2-difluoro-ethyl)-piperazine-1-carboxylic acid tert-butyl ester 

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