Benzaldehyde → Ethyl 2,2-difluoro-3-hydroxy-3-phenylpropanoate

HRID 520422Notes

Reaction equation

HRID 520422 reaction equation
[CH:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:10]([F:17])([F:16])[C:11]([O:13][CH2:14][CH3:15])=[O:12].C1COCC1>CCOCC.[Zn]>[F:16][C:10]([F:17])([CH:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:11]([O:13][CH2:14][CH3:15])=[O:12]

Participants

6

Reactant 3

HCID 240BenzaldehydeHCID 8028TetrahydrofuranHCID 69585Ethyl bromodifluoroacetate

Product 1

HCID 11138943Ethyl 2,2-difluoro-3-hydroxy-3-phenylpropanoateYield 54%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 3283Diethyl EtherSolvent

Procedure

A stirred suspension of zinc (0.981 g, 15.00 mmol) in a solution of benzaldehyde (0.531 g, 5 mmol) and ethyl 2-bromo-2,2-difluoroacetate (1.522 g, 7.50 mmol) in an. THF (10 mL) was sonicated for 4-5 h and then stirred at rt overnight. The reaction was cooled and diluted with ether and washed with 1 N HCl, water, brine and dried (MgSO4). Evaporation of solvents afforded a clear oil which was purified by silica gel FCC (0-10% EtOAc in DCM) to afford ethyl 2,2-difluoro-3-hydroxy-3-phenylpropanoate as a clear oil (619 mg, ˜54%). 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.49-7.44 (m, 2H), 7.43-7.39 (m, 3H), 5.23-5.12 (m, J=15.3, 8.0, 5.5 Hz, 1H), 4.32 (q, J=7.1 Hz, 2H), 2.87-2.76 (m, 1H), 1.31 (t, J=7.2 Hz, 3H).

Workup

  1. temperatureThe reaction was cooled
  2. washwashed with 1 N HCl, water, brine
  3. dry with materialdried (MgSO4)
  4. customEvaporation of solvents
  5. customafforded a clear oil which
  6. customwas purified by silica gel FCC (0-10% EtOAc in DCM)

Sources & evidence

ORD record
ord-42c1c115daab46ce9e30eddebc29c298
Source dataset
uspto-grants-2016_05
Patent number
US09326973B2

Reaction notes

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