Benzyl(methoxymethyl)((trimethylsilyl)methyl)amine → trans-Ethyl 1-benzyl-4-phenylpyrrolidine-3-carboxylate

HRID 722393

Reaction equation

HRID 722393 reaction equation
[C:1]([O:11][CH2:12][CH3:13])(=[O:10])/[CH:2]=[CH:3]/[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.CO[CH2:16][N:17]([CH2:25][Si](C)(C)C)[CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>ClCCl.FC(F)(F)C(O)=O>[CH2:12]([O:11][C:1]([C@H:2]1[C@H:3]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:25][N:17]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:16]1)=[O:10])[CH3:13]

Participants

5

Reactant 2

HCID 353442Benzyl(methoxymethyl)((trimethylsilyl)methyl)amine3×HCID 637758Ethyl Cinnamate

Product 1

HCID 12922288trans-Ethyl 1-benzyl-4-phenylpyrrolidine-3-carboxylateYield 48%

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidCatalyst3×HCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a mixture of ethyl trans-cinnamate (2 g, 11.4 mmol) and N-(methoxymethyl)(phenyl)-N-((trimethylsilyl)methyl)methanamine (2.37 mL) in dichloromethane (18 mL) was added 3 drops of trifluoroacetic acid and the mixture was stirred at 40° C. for 45 min. Then another 0.56 mL of N-(methoxymethyl)(phenyl)-N-((trimethylsilyl) methyl)methanamine and 1 drop of trifluoroacetic acid were added and the mixture was stirred at 40° C. for another 45 min. Then another 0.26 mL of N-(methoxymethyl)(phenyl)-N-((trimethylsilyl)methyl)methanamine and 1 drop of trifluoroacetic acid were added and the mixture was stirred at 40° C. for overnight. After cooling down to room temperature, the mixture was concentrated under vacuum and purified by Flash Chromatography with from 8% ethyl acetate/92% hexane to 10% ethyl acetate/90% hexane over 20 min. to give the title compound as a clear colorless sticky oil (1.69 g, 48% yield). 1H NMR (400 MHz, CDCl3) δ 1.20 (3H, t, J=6.4, 9.6 Hz), 2.86 (1H, m), 3.00 (1H, t, J=9.6 Hz), 3.04–3.07 (2H, m), 3.65–3.68 (3H, m), 4.09–4.13 (2H, m), 7.19–7.37 (10H, m). HPLC purity (retention time): 93% (1.30 min, method C). MS: 310.30 (MH+).

Workup

  1. stirringthe mixture was stirred at 40° C. for another 45 min
  2. stirringthe mixture was stirred at 40° C. for overnight
  3. temperatureAfter cooling down to room temperature
  4. concentrationthe mixture was concentrated under vacuum
  5. custompurified by Flash Chromatography with from 8% ethyl acetate/92% hexane to 10% ethyl acetate/90% hexane over 20 min.

Sources & evidence

ORD record
ord-cd6efc493d4f4e579445879a6b0601e1
Source dataset
uspto-grants-2006_11
Patent number
US07138423B2

Linked notes

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