Aluminium lithium hydride → 2-(4-Chlorophenyl)-2,2-difluoroethanol

HRID 54250Notes

Reaction equation

HRID 54250 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:21])([F:20])[C:15](OCC)=[O:16])=[CH:10][CH:9]=1>C(OCC)C>[F:21][C:14]([F:20])([C:11]1[CH:12]=[CH:13][C:8]([Cl:7])=[CH:9][CH:10]=1)[CH2:15][OH:16]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 21468011Ethyl 2-(4-Chlorophenyl)-2,2-difluoroacetate

Product 1

HCID 232378442-(4-Chlorophenyl)-2,2-difluoroethanol

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
25 °C

Procedure

Lithium aluminum hydride, 2.4 grams (0.063 mole), is placed in a reaction vessel, and 200 mL of diethyl ether is added dropwise with stirring. To this is added dropwise a solution of 22.8 grams (0.097 mole) of ethyl 4-chlorophenyldifluoroacetate (prepared by methods taught by W. J. Middleton et al., J. Org. Chem., (1980), 45, 2883-2887) in 100 mL of diethyl ether, while maintaining the reaction mixture temperature at about 25° C. Upon completion of addition, the reaction mixture is stirred at ambient temperature for about 36 hours. The reaction is then quenched by the careful dropwise addition of an aqueous solution of 10% sodium hydroxide. The reaction mixture is slowly made acidic with aqueous 2N hydrochloric acid and then is diluted with 200 mL of water. The organic layer is separated, and the aqueous layer is washed with two 300 mL portions of diethyl ether. The organic layer and the diethyl ether washes are combined and washed with one 250 mL portion of an aqueous solution saturated with sodium chloride. The organic layer is dried with magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure, yielding 2,2-difluoro-2-(4-chlorophenyl)ethanol.

Workup

  1. additionUpon completion of addition
  2. stirringthe reaction mixture is stirred at ambient temperature for about 36 hours
  3. customThe reaction is then quenched by the careful dropwise addition of an aqueous solution of 10% sodium hydroxide
  4. additionis diluted with 200 mL of water
  5. customThe organic layer is separated
  6. washthe aqueous layer is washed with two 300 mL portions of diethyl ether
  7. washwashed with one 250 mL portion of an aqueous solution saturated with sodium chloride
  8. dry with materialThe organic layer is dried with magnesium sulfate
  9. filtrationfiltered
  10. concentrationThe filtrate is concentrated under reduced pressure

Sources & evidence

ORD record
ord-70bad8e5400b4f1ea01fe9649e17ad86
Source dataset
uspto-grants-1997_04
Patent number
US05622954

Reaction notes

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