Trimethylsilyldiazomethane → (R)-2-benzyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

HRID 1894987Notes

Reaction equation

HRID 1894987 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@@:9]1([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:13]([OH:15])=[O:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Si](C=[N+]=[N-])(C)(C)[CH3:24]>C1COCC1.CO>[CH3:24][O:14][C:13]([C@:9]1([CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:10][CH2:11][CH2:12][N:8]1[C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])=[O:15]

Participants

5

Reactant 2

HCID 167693TrimethylsilyldiazomethaneHCID 2761823(R)-2-Benzyl-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid

Product 1

HCID 66687350(R)-2-benzyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl esterYield 81%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (R)-2-benzyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (1.23 g, 4.0 mmol) in THF (10 mL) and methanol (10 mL) at 0° C. under nitrogen was added TMS-diazomethane (5.0 mL of a 2.0 M solution in hexanes, 5.0 mmol) dropwise. The reaction mixture was warmed to ambient temperature then concentrated in vacuo to an oil (1.36 g). Purification by chromatography (silica, 5-15% EtOAc in hexanes) gave (R)-2-benzyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (1.03 g, 3.23 mmol, 81%) as an oil.

Workup

  1. concentrationthen concentrated in vacuo to an oil (1.36 g)
  2. customPurification by chromatography (silica, 5-15% EtOAc in hexanes)

Sources & evidence

ORD record
ord-a1594afe5c4646629adc5f95b5bd7af6
Source dataset
uspto-grants-2013_08
Patent number
US08513425B2

Reaction notes

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