2-Benzylsulfanylmethylacrylic acid → 2-Benzylsulfanylmethyl-3-[2-(1,1-difluoro-methoxy)-benzylsulfanyl]-propionic acid

HRID 1830119Notes

Reaction equation

HRID 1830119 reaction equation
[F:1][CH:2]([F:12])[O:3][C:4]1[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=1[CH2:6][SH:7].[CH2:13]([S:20][CH2:21][C:22](=[CH2:26])[C:23]([OH:25])=[O:24])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>CN(C)C1C=CN=CC=1.CN(C=O)C>[CH2:13]([S:20][CH2:21][CH:22]([CH2:26][S:7][CH2:6][C:5]1[CH:8]=[CH:9][CH:10]=[CH:11][C:4]=1[O:3][CH:2]([F:12])[F:1])[C:23]([OH:25])=[O:24])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

5

Reactant 2

HCID 220539822-Benzylsulfanylmethylacrylic acidHCID 22054104[2-(Difluoromethoxy)phenyl]methanethiol2×

Product 1

HCID 220539802-Benzylsulfanylmethyl-3-[2-(1,1-difluoro-methoxy)-benzylsulfanyl]-propionic acidYield 63%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of 2-difluoromethoxybenzyl mercaptan (0.534 g, 2.81 mmol), 2-benzylsulfanylmethyl-acrylic acid (0.585 g, 2.81 mmol) and 4-dimethylaminopyridine (36 mg, 0.3 mmol) in DMF (1.5 ml) was stirred at room temperature for 20 hours. An additional amount of 2-difluoromethoxybenzyl mercaptan (0.201 g) was added to the reaction mixture and stirring was continued for another 24 hours. The reaction mixture was poured into dilute, cold, aqueous HCl and the product extracted with ethyl acetate. The extracts were washed with saturated aqueous sodium chloride and then dried over magnesium sulfate. The solvent was removed by rotary evaporation at reduced pressure and the residue was chromatographed on silica gel eluting with ethyl acetate/hexane to give 2-Benzylsulfanylmethyl-3-[2-(1,1-difluoro-methoxy)-benzylsulfanyl]-propionic acid (0.706 g).

Workup

  1. additionThe reaction mixture was poured
  2. additioninto dilute
  3. extractioncold, aqueous HCl and the product extracted with ethyl acetate
  4. washThe extracts were washed with saturated aqueous sodium chloride
  5. dry with materialdried over magnesium sulfate
  6. customThe solvent was removed by rotary evaporation at reduced pressure
  7. customthe residue was chromatographed on silica gel eluting with ethyl acetate/hexane

Sources & evidence

ORD record
ord-78f659bb8cf445b49e76319e3f6c517f
Source dataset
uspto-grants-2006_06
Patent number
US07064123B1

Reaction notes

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