Hydrochloric Acid → 1-tert-Butyl 2-methyl (2S,4R)-4-((methanesulfonyl)oxy)pyrrolidine-1,2-dicarboxylate

HRID 1034490Notes

Reaction equation

HRID 1034490 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:15][C@H:14]([OH:16])[CH2:13][C@H:9]1[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:17](N(CC)CC)C.[CH3:24][S:25](Cl)(=[O:27])=[O:26].Cl>O1CCCC1.CO>[CH3:17][O:11][C:10]([C@@H:9]1[CH2:13][C@@H:14]([O:16][S:25]([CH3:24])(=[O:27])=[O:26])[CH2:15][N:8]1[C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])=[O:12]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8471Triethylamine2×HCID 31297Methanesulfonyl chlorideHCID 88804(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid

Product 1

HCID 147726821-tert-Butyl 2-methyl (2S,4R)-4-((methanesulfonyl)oxy)pyrrolidine-1,2-dicarboxylateYield 77%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of trans-1-t-butoxycarbonyl-4-hydroxy-L-proline (8.5 g) in tetrahydrofuran (110 ml) at -30° C., triethylamine (12.8 ml) and methanesulfonyl chloride (6.27 ml) are added. The mixture is stirred at the same temperature for 30 minutes. To the mixture triethylamine (5.13 ml) and methanol (30 ml) are added. The mixture is stirred for 30 minutes. The reaction mixture is acidified with 1N-hydrochloric acid (37 ml) and extracted with ethyl acetate. The extract is successively washed with water, aqueous sodium hydrogen carbonate, water and saturated brine, dried over sodium sulfate, and concentrated in vacuo. The residue is purified by silica gel column chromatography and recrystallized from toluene-petroleum ether to give (2S,4R)-1-t-butoxycarbonyl-4-methanesulfonyloxypyrrolidine-2-carboxylic acid methyl ester (9.16 g). Colorless crystals. Yield: 77%. mp. 86° to 87° C. NMR δ(CDCl3) ppm: 1.42, 1.47, 1.50(3×s, 9H), 2.19 to 2.35(m, 1H), 2.48 to 2.75(m, 1H), 3.06, 3.07, 3.26(3×s, 3H), 3.59 to 4.12(m, 5H), 4.35 to 4.60(m, 1H), 5.18 to 5.32(m, 1H). IR ν (CHCl3) cm-1 : 1748, 1698.

Workup

  1. stirringThe mixture is stirred for 30 minutes
  2. extractionextracted with ethyl acetate
  3. washThe extract is successively washed with water, aqueous sodium hydrogen carbonate, water and saturated brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by silica gel column chromatography
  7. customrecrystallized from toluene-petroleum ether

Sources & evidence

ORD record
ord-2665ce59c121434680b14d7906329321
Source dataset
uspto-grants-1994_05
Patent number
US05317016

Reaction notes

Loading…