Benzyl(methoxymethyl)((trimethylsilyl)methyl)amine → Benzyl (3RS,4SR)-1-benzyl-4-methylpyrrolidine-3-carboxylate

HRID 445992Notes

Reaction equation

HRID 445992 reaction equation
[C:1]([O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)(=[O:5])/[CH:2]=[CH:3]/[CH3:4].CO[CH2:16][N:17]([CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH2:18][Si](C)(C)C>ClCCl.FC(F)(F)C(O)=O>[CH2:23]([N:17]1[CH2:16][CH:3]([CH3:4])[CH:2]([C:1]([O:6][CH2:7][C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)=[O:5])[CH2:18]1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

5

Reactant 2

HCID 353442Benzyl(methoxymethyl)((trimethylsilyl)methyl)amineHCID 5356259Benzyl crotonate, (E)-

Product 1

HCID 86678243Benzyl (3RS,4SR)-1-benzyl-4-methylpyrrolidine-3-carboxylateYield 105.9%

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidCatalystHCID 6344DichloromethaneSolvent

Procedure

Benzyl (2E)-but-2-enoate obtained in Example 1e (20.5 g, 116 mmol) was dissolved in dichloromethane (5 ml), and the mixture was cooled in an ice bath with stirring. Trifluoroacetic acid (257 μl, 3.47 mmol) was added, and N-(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine (33.1 g, 139 mmol) was added dropwise to the reaction liquid over 15 minutes so that the internal temperature did not exceed 62° C., while washing with dichloromethane (25 ml). The reaction liquid was left to stand until it reached mom temperature and was stirred for 15 hours. The reaction liquid was concentrated and purified by silica gel column chromatography (elution solvent: ethyl acetate/heptane) to give the title compound (38 g).

Workup

  1. temperaturethe mixture was cooled in an ice bath
  2. customdid not exceed 62° C.
  3. washwhile washing with dichloromethane (25 ml)
  4. customThe reaction liquid
  5. waitwas left
  6. stirringwas stirred for 15 hours
  7. customThe reaction liquid
  8. concentrationwas concentrated
  9. custompurified by silica gel column chromatography (elution solvent: ethyl acetate/heptane)

Sources & evidence

ORD record
ord-da6d19fbe0344d7b839b55a9cac26898
Source dataset
uspto-grants-2013_07
Patent number
US08476301B2

Reaction notes

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