Trifluoroacetic acid → 3-Pyrrolidinecarboxylic acid, 4-cyclopropyl-1-(phenylmethyl)-, methyl ester

HRID 1162723Notes

Reaction equation

HRID 1162723 reaction equation
[CH2:1]([N:8]([CH2:12][Si](C)(C)C)[CH2:9]OC)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:17][O:18][C:19](=[O:25])/[CH:20]=[CH:21]/[CH:22]1[CH2:24][CH2:23]1.C(O)(C(F)(F)F)=O.C1CCCCC1>C(Cl)Cl.C1CCCCC1.CCOC(C)=O>[CH3:17][O:18][C:19]([CH:20]1[CH:21]([CH:22]2[CH2:24][CH2:23]2)[CH2:9][N:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:12]1)=[O:25]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8078CyclohexaneHCID 353442Benzyl(methoxymethyl)((trimethylsilyl)methyl)amineHCID 1458555198272-33-4

Product 1

HCID 686476703-Pyrrolidinecarboxylic acid, 4-cyclopropyl-1-(phenylmethyl)-, methyl esterYield 32.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent4×HCID 21867204Cyclohexane ethylacetateSolvent

Procedure

101.1 To a stirred, cooled (0° C.) solution of 3.18 g N-benzyl-N-(methoxymethyl)trimethyl-silylmethylamine (CAS 93102-05-7) in 30 ml CH2Cl2 under an argon atmosphere was added dropwise a solution of 1.69 g (E)-3-cyclopropyl-acrylic acid methyl ester (CAS 59939-11-6; J. Org. Chem. 1990, 55(10), 3097) in 15 ml CH2Cl2 over a period of 20 min. Then a solution of 0.1 ml TFA in 5 ml CH2Cl2 was added dropwise within 10 min. When addition was complete, the mixture (slowly warming up to room temperature) was stirred overnight. Then, the mixture was diluted with CH2Cl2, washed with sat. aq. NaHCO3 and brine, dried over MgSO4, filtered and concentrated. The crude product was isolated by chromatography (silica gel; (gradient: cyclohexane->cyclohexane/EtOAc 7:3) to give 1.14 g (3RS,4RS)-1-benzyl-4-cyclopropyl-pyrrolidine-3-carboxylic acid methyl ester as light yellow oil. MS 260.3 ([M+H]+)

Workup

  1. additionWhen addition
  2. washwashed with sat. aq. NaHCO3 and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was isolated by chromatography (silica gel

Sources & evidence

ORD record
ord-d510df7ec5e74d2c98518136a1e9ba86
Source dataset
uspto-grants-2010_10
Patent number
US07820699B2

Reaction notes

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