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Trifluoroacetic acid → 1-Benzyl-3-dimethylaminomethyl-pyrrolidine-3-carboxylic acid methyl ester

HRID 1038074
Notes
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Reaction equation

HRID 1038074 reaction equation
[CH3:1][O:2][C:3](=[O:10])[C:4]([CH2:6][N:7]([CH3:9])[CH3:8])=[CH2:5].CO[CH2:13][N:14]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH2:15][Si](C)(C)C.FC(F)(F)C(O)=O.C([O-])(O)=O.[Na+]>ClCCl>[CH3:1][O:2][C:3]([C:4]1([CH2:6][N:7]([CH3:9])[CH3:8])[CH2:5][CH2:13][N:14]([CH2:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:15]1)=[O:10]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 353442Benzyl(methoxymethyl)((trimethylsilyl)methyl)amineHCID 516892Sodium BicarbonateHCID 206696872-Dimethylaminomethyl-acrylic acid methyl ester

Product 1

HCID 576861841-Benzyl-3-dimethylaminomethyl-pyrrolidine-3-carboxylic acid methyl esterYield 78%

Reagents, catalysts & solvents

1
HCID 6344DichloromethaneSolvent2×

Procedure

To a cold solution of 2-dimethylaminomethyl-acrylic acid methyl ester (0.266 g, 1.86 mmol) and N-(methoxymethyl)-N-(trimethylsilylmethyl)benzyl-amine (1.43 ml, 5.59 mmol) in dichloromethane (25 ml) was added at 0° C. trifluoroacetic acid (83 μl, 1.12 mmol). The resulting solution was warmed to room temperature and stirred for 72 hours. Saturated aq. NaHCO3 (60 ml) was added to the reaction mixture and stirred for 10 minutes. Diluted with dichloromethane (50 ml) and the organic layer was separated. The organic layer was dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography on silica get eluting with a solution of ethyl acetate in hexanes (1:2) followed by CH2Cl2/MeOH/NH4OH (9/1/0.01) to give the title compound (400 mg, 78%).

Workup

  1. stirringstirred for 10 minutes
  2. customthe organic layer was separated
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by column chromatography on silica
  7. customget
  8. washeluting with a solution of ethyl acetate in hexanes (1:2)

Sources & evidence

ORD record
ord-88c25da0e3c54578a03b0f68e8958b8b
Source dataset
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08546404B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes