Trifluoroacetic acid → (+/-)-cis-Methyl 1-benzyl-4-(2-(isopropoxycarbonyl)-3-(trifluoromethyl)phenyl)pyrrolidine-3-carboxylate

HRID 2100565Notes

Reaction equation

HRID 2100565 reaction equation
[CH3:1][O:2][C:3](=[O:22])/[CH:4]=[CH:5]\[C:6]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[C:7]=1[C:8]([O:10][CH:11]([CH3:13])[CH3:12])=[O:9].CO[CH2:25][N:26]([CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[CH2:27][Si](C)(C)C.FC(F)(F)C(O)=O>CCOC(C)=O.FC(F)(F)C(O)=O>[CH2:32]([N:26]1[CH2:27][C@H:5]([C:6]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[C:7]=2[C:8]([O:10][CH:11]([CH3:13])[CH3:12])=[O:9])[C@H:4]([C:3]([O:2][CH3:1])=[O:22])[CH2:25]1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 353442Benzyl(methoxymethyl)((trimethylsilyl)methyl)amine2×HCID 69052122HCID 69052122, compound

Product 1

HCID 131727564(+/-)-cis-Methyl 1-benzyl-4-(2-(isopropoxycarbonyl)-3-(trifluoromethyl)phenyl)pyrrolidine-3-carboxylateYield 93%

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidCatalystHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
65 °C

Procedure

To a solution of (Z)-isopropyl 2-(3-methoxy-3-oxoprop-1-enyl)-6-(trifluoromethyl)benzoate (2.5 g, 7.9 mmol) in 30 mL of EtOAc was added N-(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine (2.34 g, 9.9 mmol) and trifluoroacetic acid (0.12 mL, 1.6 mmol). The solution was allowed to stir at 65° C. for 4 h. Starting material still remained by TLC analysis and so additional N-(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine (1.0 g, 4.2 mmol) and trifluoroacetic acid (0.05 mL, 0.65 mmol) were added and the reaction was stirred at 65° C. for an additional 3 h. The reaction was allowed to cool and was diluted with EtOAc, washed with sat'd aq NaHCO3 and brine, dried (MgSO4) and concentrated. The residue was purified by flash chromatography (5:1 hexane/EtOAc) to afford 3.3 g (93%) of the title compound as an oil. LRMS (ES)+: 450.35 (M+H)+.

Workup

  1. additionwere added
  2. stirringthe reaction was stirred at 65° C. for an additional 3 h
  3. temperatureto cool
  4. washwashed with sat'd aq NaHCO3 and brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography (5:1 hexane/EtOAc)

Sources & evidence

ORD record
ord-0e84824028dc404ca3c2d9235fc05014
Source dataset
uspto-grants-2009_08
Patent number
US07572805B2

Reaction notes

Loading…