Trifluoroacetic acid → (+/-)-trans-Benzyl 1-benzyl-4-(2-(methoxycarbonyl)-3-(trifluoromethyl)phenyl)pyrrolidine-3-carboxylate

HRID 2100576Notes

Reaction equation

HRID 2100576 reaction equation
[CH2:1]([O:8][C:9](=[O:26])/[CH:10]=[CH:11]/[C:12]1[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:25])([F:24])[F:23])[C:13]=1[C:14]([O:16][CH3:17])=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO[CH2:29][N:30]([CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[CH2:31][Si](C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl.CCOC(C)=O.COCN(CC1C=CC=CC=1)C[Si](C)(C)C.FC(F)(F)C(O)=O>[CH2:36]([N:30]1[CH2:31][C@@H:11]([C:12]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:24])([F:25])[F:23])[C:13]=2[C:14]([O:16][CH3:17])=[O:15])[C@H:10]([C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[O:26])[CH2:29]1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

8

Reactant 3

HCID 6422Trifluoroacetic acidHCID 353442Benzyl(methoxymethyl)((trimethylsilyl)methyl)amineHCID 69055523HCID 69055523, compound

Product 1

HCID 131727567(+/-)-trans-Benzyl 1-benzyl-4-(2-(methoxycarbonyl)-3-(trifluoromethyl)phenyl)pyrrolidine-3-carboxylateYield 95.5%

Reagents, catalysts & solvents 4

HCID 6422Trifluoroacetic acidCatalystHCID 353442Benzyl(methoxymethyl)((trimethylsilyl)methyl)amineCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (E)-methyl 2-(3-(benzyloxy)-3-oxoprop-1-enyl)-6-(trifluoromethyl)benzoate (5.83 g, 16.0 mmol) in 60 mL of CH2Cl2 was added N-(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine (4.0 g, 16.8 mmol) and trifluoroacetic acid (0.25 mL, 3.2 mmol). The solution was allowed to stir at ambient temperature for 18 h. Starting material still remained by TLC analysis and so additional N-(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine (0.25 g, 1.05 mmol) and trifluoroacetic acid (0.05 mL, 0.65 mmol) were added and the reaction was stirred at 40° C. for an additional 2 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 (4:1 hexane/EtOAc) to afford 7.6 g (95%) of the title compound as an oil. LRMS (ES)+: 498.32 (M+H)+.

Workup

  1. additionwere added
  2. stirringthe reaction was stirred at 40° C. for an additional 2 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 (4:1 hexane/EtOAc)

Sources & evidence

ORD record
ord-bce74ba8d2fb4184860671c4bcc09dd2
Source dataset
uspto-grants-2009_08
Patent number
US07572805B2

Reaction notes

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