Cyclohexanone → Ethyl α,α-difluoro-1-hydroxycyclohexaneacetate

HRID 520415Notes

Reaction equation

HRID 520415 reaction equation
[C:1]1(=[O:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Br[C:9]([F:16])([F:15])[C:10]([O:12][CH2:13][CH3:14])=[O:11].C1COCC1>CCOCC.[Zn]>[F:15][C:9]([F:16])([C:1]1([OH:7])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)[C:10]([O:12][CH2:13][CH3:14])=[O:11]

Participants

6

Reactant 3

HCID 7967CyclohexanoneHCID 8028TetrahydrofuranHCID 69585Ethyl bromodifluoroacetate

Product 1

HCID 10933036Ethyl α,α-difluoro-1-hydroxycyclohexaneacetateYield 70%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 3283Diethyl EtherSolvent

Procedure

A stirred suspension of zinc (0.981 g, 15.01 mmol) in a solution of cyclohexanone (0.491 g, 5.0 mmol) and ethyl 2-bromo-2,2-difluoroacetate (2.031 g, 10.01 mmol) in an. THF (5 mL) was sonicated for 4-5 h and then heated to reflux for 1-2 h. The reaction mixture was cooled and diluted with ether and washed with 1 N HCl, satd. NaHCO3, water, brine and dried (MgSO4). Evaporation of solvents afforded an oil which was purified by silica gel FCC (5-10% EtOAc in DCM) to afford ethyl 2,2-difluoro-2-(1-hydroxycyclohexyl)acetate as a clear oil (770 mg, ˜70%). 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 4.37 (q, J=7.2 Hz, 2H), 2.10-2.01 (m, J=3.4 Hz, 1H), 1.82-1.69 (m, 3H), 1.68-1.54 (m, 6H), 1.38 (t, J=7.2 Hz, 3H), 1.20 (br. s, 1H).

Workup

  1. temperatureheated
  2. temperatureto reflux for 1-2 h
  3. temperatureThe reaction mixture was cooled
  4. washwashed with 1 N HCl
  5. dry with materialNaHCO3, water, brine and dried (MgSO4)
  6. customEvaporation of solvents
  7. customafforded an oil which
  8. customwas purified by silica gel FCC (5-10% EtOAc in DCM)

Sources & evidence

ORD record
ord-96b711cfbb3144fab35b37aeb5136de1
Source dataset
uspto-grants-2016_05
Patent number
US09326973B2

Reaction notes

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