Trimethylsilyldiazomethane → 1-tert-Butyl 2-methyl (2R,4S)-4-hydroxypyrrolidine-1,2-dicarboxylate

HRID 1443002Notes

Reaction equation

HRID 1443002 reaction equation
[CH3:1][Si](C=[N+]=[N-])(C)C.[C:8]([O:12][C:13]([N:15]1[CH2:22][C@@H:21]([OH:23])[CH2:20][C@@H:16]1[C:17]([OH:19])=[O:18])=[O:14])([CH3:11])([CH3:10])[CH3:9]>C(Cl)Cl.CO>[OH:23][C@@H:21]1[CH2:22][N:15]([C:13]([O:12][C:8]([CH3:11])([CH3:9])[CH3:10])=[O:14])[C@@H:16]([C:17]([O:19][CH3:1])=[O:18])[CH2:20]1

Participants

5

Reactant 2

HCID 167693TrimethylsilyldiazomethaneHCID 688615N-Boc-4-hydroxy-D-proline, trans-

Product 1

HCID 69512011-tert-Butyl 2-methyl (2R,4S)-4-hydroxypyrrolidine-1,2-dicarboxylateYield 97%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

(Trimethylsilyl)diazomethane (2N solution in hexane, 2.9 ml) was added dropwise over 5 minutes to a stirred solution of (4S)-1-(tert-butoxycarbonyl)-4-hydroxy-D-proline (1.0 g) in DCM (20 ml) and methanol (5 ml) at room temperature until a permanent faint yellow colour persisted. The reaction mixture was concentrated in vacuo and purified by column chromatography, using 0-50% ethyl acetate in hexane as eluent, to give 1-tert-butyl 2-methyl (2R,4S)-4-hydroxypyrrolidine-1,2-dicarboxylate as a clear oil (1.03 g, 97%); NMR spectrum (CDCl3) 4.90-4.37 (m, 2H), 3.73 (s, 3H), 3.64 (dd, 1H), 3.53-3.43 (m, 1H), 2.34-2.27 (m, 1H), 2.12-1.97 (m, 2H), 1.46 (s, 3H), 1.41 (s, 6H).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. custompurified by column chromatography

Sources & evidence

ORD record
ord-05753a76d55842ce8d13fa774602d831
Source dataset
uspto-grants-2010_02
Patent number
US07659279B2

Reaction notes

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