Trifluoroacetic acid → methyl (3R*,4S*)-1-benzyl-4-(3,4-dichlorophenyl)pyrrolidine-3-carboxylate

HRID 1260921Notes

Reaction equation

HRID 1260921 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:11]=[CH:12][C:13]=1[Cl:14])[CH:5]=[CH:6][C:7]([O:9][CH3:10])=[O:8].CO[CH2:17][N:18]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH2:19][Si](C)(C)C.FC(F)(F)C(O)=O.C(OCC)(=O)C>C1(C)C=CC=CC=1>[CH2:24]([N:18]1[CH2:19][C@H:5]([C:4]2[CH:11]=[CH:12][C:13]([Cl:14])=[C:2]([Cl:1])[CH:3]=2)[C@@H:6]([C:7]([O:9][CH3:10])=[O:8])[CH2:17]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8857Ethyl AcetateHCID 353442Benzyl(methoxymethyl)((trimethylsilyl)methyl)amineHCID 54151376Methyl 3-(3,4-dichlorophenyl)prop-2-enoate

Product 1

HCID 67232866methyl (3R*,4S*)-1-benzyl-4-(3,4-dichlorophenyl)pyrrolidine-3-carboxylateYield 103.9%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To a solution of the compound (20.4 g) obtained in step 1 and N-(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine (22.0 g) in toluene (180 mL) was added a solution of trifluoroacetic acid (1.31 mL) in toluene (18 mL) at 0° C., and the mixture was stirred at room temperature for 14 hr. To the reaction mixture was added ethyl acetate (300 mL), and the mixture was washed with saturated aqueous sodium hydrogen carbonate solution, water and brine and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 10→25% ethyl acetate/hexane) to give methyl (3R*,4S*)-1-benzyl-4-(3,4-dichlorophenyl)pyrrolidine-3-carboxylate (33.4 g, 100%) as a pale yellow oil.

Workup

  1. washthe mixture was washed with saturated aqueous sodium hydrogen carbonate solution, water and brine
  2. customdried
  3. customthe solvent was evaporated under reduced pressure
  4. customThe obtained residue was purified by silica gel column chromatography (solvent gradient; 10→25% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-afa5e98109884619a51f22f859cc0263
Source dataset
uspto-grants-2013_06
Patent number
US08470816B2

Reaction notes

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