Trifluoroacetic acid → Dimethyl 1-benzylpyrrolidine-3,4-dicarboxylate

HRID 712436Notes

Reaction equation

HRID 712436 reaction equation
[C:1]([O:9][CH3:10])(=[O:8])/[CH:2]=[CH:3]\[C:4]([O:6][CH3:7])=[O: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.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:20]([N:14]1[CH2:15][CH:3]([C:4]([O:6][CH3:7])=[O:5])[CH:2]([C:1]([O:9][CH3:10])=[O:8])[CH2:13]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 353442Benzyl(methoxymethyl)((trimethylsilyl)methyl)amineHCID 5271565Dimethyl maleate

Product 1

HCID 13120109Dimethyl 1-benzylpyrrolidine-3,4-dicarboxylateYield 86.02%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of dimethyl maleate (4.00 g) in CH2Cl2 (100 mL) was added N-(methoxymethyl)-N-(trimethylsilylmethyl)benzylamine (1.2 eq) followed by a solution of TFA in CH2Cl2 (0.1 eq, 1 M) dropwise at 0° C. under N2. The reaction mixture was heated to room temperature and stirred for 6 h, washed with water followed by brine. The mixture was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was chromatographed with a silica gel column (eluting agent: 3:1 (v/v) PE/EA) to yield the title compound (6.62 g, 86.02%). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 278 (M+1); 1H NMR (400 MHz, CDCl3) δ: 2.70-2.75 (m, 2H), 3.12-3.17 (m, 1H), 3.30-3.33 (m, 2H), 3.66 (s, 6H), 7.24-7.31 (m, 5H).

Workup

  1. washwashed with water
  2. dry with materialThe mixture was dried over anhydrous Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was chromatographed with a silica gel column (eluting agent: 3:1 (v/v) PE/EA)

Sources & evidence

ORD record
ord-46f86791b85d4af99dfebbca27a377a6
Source dataset
uspto-grants-2015_11
Patent number
US09181277B2

Reaction notes

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