Trifluoroacetic acid → 3-Pyrrolidinecarboxylic acid, 1-(phenylmethyl)-4-(2,2,2-trifluoroethyl)-, ethyl ester, (3R,4R)-rel-

HRID 577718Notes

Reaction equation

HRID 577718 reaction equation
[F:1][C:2]([F:12])([F:11])[CH2:3]/[CH:4]=[CH:5]/[C:6]([O:8][CH2:9][CH3:10])=[O:7].C(O)(C(F)(F)F)=O.[CH2:20]([N:27]([CH2:33]O)[CH2:28][Si](C)(C)C)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C(Cl)Cl>[CH2:20]([N:27]1[CH2:33][C@@H:4]([CH2:3][C:2]([F:11])([F:12])[F:1])[C@H:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH2:28]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 15104041Ethyl 5,5,5-trifluoropent-2-enoate2×HCID 70869782HCID 70869782, compound

Product 1

HCID 575562183-Pyrrolidinecarboxylic acid, 1-(phenylmethyl)-4-(2,2,2-trifluoroethyl)-, ethyl ester, (3R,4R)-rel-Yield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of ethyl (2E)-5,5,5-trifluoropent-2-enoate (3.0 g, 16.5 mmol) and TFA (0.38 g, 3.3 mmol) in DCM (40 mL) was added dropwise {benzyl[(trimethylsilyl)methyl]amino}methanol (7.8 g, 33 mmol) at 0° C. over a period of 30 min. After the addition, the mixture was refluxed overnight. TLC (petroleum ether:EtOAc 10:1) indicated ethyl (2E)-5,5,5-trifluoropent-2-enoate was consumed. The reaction mixture was washed with sat. NaHCO3 (40 mL), brine (40 mL), dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (silica gel, petroleum ether:EtOAc=100:1 to 10:1) to give the title compound (5.1 g, 98% yield) as a yellow oil.

Workup

  1. additionAfter the addition
  2. temperaturethe mixture was refluxed overnight
  3. customwas consumed
  4. washThe reaction mixture was washed with sat. NaHCO3 (40 mL), brine (40 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (silica gel, petroleum ether:EtOAc=100:1 to 10:1)

Sources & evidence

ORD record
ord-32089947bf5240b89045271dcf6c6daf
Source dataset
uspto-grants-2015_05
Patent number
US09040547B2

Reaction notes

Loading…