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

HRID 2047438Notes

Reaction equation

HRID 2047438 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 solution was added ethyl acetate (300 mL), and the mixture was washed with saturated aqueous sodium hydrogen carbonate solution, water and saturated 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 saturated 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-02e2525ad34c485c847aba329ddbc476
Source dataset
uspto-grants-2013_11
Patent number
US08592454B2

Reaction notes

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