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

HRID 885563Notes

Reaction equation

HRID 885563 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].Cl>O1CCCC1.C(OCC)C.[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

7

Reactant 3

HCID 240BenzaldehydeHCID 313Hydrochloric AcidHCID 69585Ethyl bromodifluoroacetate

Product 1

HCID 11138943Ethyl 2,2-difluoro-3-hydroxy-3-phenylpropanoate

Reagents, catalysts & solvents 3

HCID 23994ZincCatalyst2×HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of benzaldehyde (3.0 g, 28 mmol) in anhydrous tetrahydrofuran (80 mL) was added zinc (2.4 g, 36 mmol). The mixture was heated at 75° C. under inert atmosphere and ethyl 2-bromo-2,2-difluoroacetate (4.4 mL, 34 mmol) was slowly added. The mixture was heated under the same conditions for 2 hours. After cooling, 2N hydrochloric acid (25 mL) was added until the complete consumption of unreacted zinc. The solvent was removed under reduced pressure. The crude reaction was dissolved in ethyl ether (150 mL) and washed with brine (2×100 mL), dried (Na2SO4), and the solvent removed under reduced pressure. The title compound was obtained (6.4 g, 99%) as yellow oil and was used in the next step without further purification.

Workup

  1. additionwas slowly added
  2. temperatureThe mixture was heated under the same conditions for 2 hours
  3. temperatureAfter cooling
  4. customThe solvent was removed under reduced pressure
  5. customThe crude reaction
  6. washwashed with brine (2×100 mL)
  7. dry with materialdried (Na2SO4)
  8. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-479dc0145d6a4e0e96129958ba02f8d7
Source dataset
uspto-grants-2012_08
Patent number
US08242177B2

Reaction notes

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