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

HRID 1506735Notes

Reaction equation

HRID 1506735 reaction equation
Br[C:2]([F:9])([F:8])[C:3]([O:5][CH2:6][CH3:7])=[O:4].BrC(Br)C.[CH:14](=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.B(OC)(OC)OC.Cl>[Zn].O1CCCC1>[F:8][C:2]([F:9])([CH:14]([OH:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4]

Participants

8

Reactant 5

HCID 240BenzaldehydeHCID 313Hydrochloric AcidHCID 8470Trimethyl borateHCID 112011,1-DibromoethaneHCID 69585Ethyl bromodifluoroacetate

Product 1

HCID 11138943Ethyl 2,2-difluoro-3-hydroxy-3-phenylpropanoateYield 61.5%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
90 °C

Procedure

A mixture of 48 g of ethyl bromodifluoroacetate, 4.5 g of dibromoethane and 50 g of tetrahydrofuran was added dropwise to a mixture of 15 g of zinc, 21 g of benzaldehyde, 60 mL of trimethyl borate, and 50 g of tetrahydrofuran at a temperature of 60° C., followed by stirring for 10 hours at 90° C. Thereafter, 100 g of 10 wt % hydrochloric acid was added to quench the reaction. By filtration, the insoluble was removed, and the filtrate was washed with saturated sodium chloride water. The reaction solution after washing was concentrated under reduced pressure. The concentrate was purified by distillation, obtaining 28 g of the target compound, ethyl 2,2-difluoro-3-hydroxy-3-phenylpropionate as colorless oily matter (yield 60%).

Workup

  1. customto quench
  2. customthe reaction
  3. filtrationBy filtration
  4. customthe insoluble was removed
  5. washthe filtrate was washed with saturated sodium chloride water
  6. washThe reaction solution after washing
  7. concentrationwas concentrated under reduced pressure
  8. distillationThe concentrate was purified by distillation

Sources & evidence

ORD record
ord-fc052c3f49d2483daeb84df51dc16d75
Source dataset
uspto-grants-2015_12
Patent number
US09221742B2

Reaction notes

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