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

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

Uses

Used in Pharmaceutical Industry:
Difluoroacetaldehyde ethyl hemiacetal is used as a chemical intermediate for the synthesis of various pharmaceuticals, contributing to the development of new drugs and improving existing ones.
Used in Organic Synthesis:
In the field of organic synthesis, difluoroacetaldehyde ethyl hemiacetal is utilized as a key building block, enabling the creation of a wide range of organic compounds with diverse applications.
Used in Research and Development:
Difluoroacetaldehyde ethyl hemiacetal is employed in research and development activities, where it aids in the discovery and innovation of new chemicals and pharmaceuticals, enhancing the scope of chemical and pharmaceutical sciences.
Used in Laboratory Settings:
DIFLUOROACETALDEHYDE ETHYL HEMIACETAL is primarily used in laboratories for its reactivity, allowing it to undergo multiple chemical reactions, which is crucial for advancing scientific knowledge and developing new chemical processes.

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

• 50562-10-2 2,2-difluoro-1-(4-methylphenyl)ethanol 
• 906559-43-1 C₉H₈ClF₂N 
• 82255-42-3 2,2-difluoro-1-phenyl-ethanol 

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