Trifluoroacetic acid → 1-Benzyl-3-methoxypyrrolidine-3-carboxylic acid methylester

HRID 1020930Notes

Reaction equation

HRID 1020930 reaction equation
[CH3:1][O:2][C:3](=[CH2:8])[C:4]([O:6][CH3:7])=[O:5].CO[CH2:11][N:12]([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH2:13][Si](C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH3:7][O:6][C:4]([C:3]1([O:2][CH3:1])[CH2:8][CH2:11][N:12]([CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:13]1)=[O:5]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 353442Benzyl(methoxymethyl)((trimethylsilyl)methyl)amineHCID 536831Methyl 2-methoxyprop-2-enoate

Product 1

HCID 537153081-Benzyl-3-methoxypyrrolidine-3-carboxylic acid methylesterYield 40%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of methyl 2-methoxyacrylate (20.8 g, 179 mmols) and N-(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine (55 ml, 215 mmols) in dichloromethane (160 ml) was added at 0° C. a solution of trifluoroacetic acid (2 ml) in dichloromethane (10 ml). The resulting solution was warmed to room temperature and stirred overnight. After concentration, the crude product was purified by column chromatography on silica gel eluting with a solution of ethyl acetate/hexanes/Et3N (1000:3000:4 to 1000:1000:3) to give the title compound (10BH) (17.7 mg, 40%). (Note: adding Et3N is essential to ensure sharp separation.)

Workup

  1. concentrationAfter concentration
  2. customthe crude product was purified by column chromatography on silica gel eluting with a solution of ethyl acetate/hexanes/Et3N (1000:3000:4 to 1000:1000:3)

Sources & evidence

ORD record
ord-64ca400a5e2543ffa3ca10505c9e77e5
Source dataset
uspto-grants-2014_05
Patent number
US08716483B2

Reaction notes

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