(2S)-1-((tert-butoxy)carbonyl)-4-methylidenepyrrolidine-2-carboxylic acid → (4S)-1-(tert-Butoxycarbonyl)-4-methyl-L-proline

HRID 1945349Notes

Reaction equation

HRID 1945349 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11](=[CH2:13])[CH2:10][C@H:9]1[C:14]([OH:16])=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2]>CC(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH3:13])[CH2:10][C@H:9]1[C:14]([OH:16])=[O:15])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

3

Reactant 1

HCID 21727417(2S)-1-((tert-butoxy)carbonyl)-4-methylidenepyrrolidine-2-carboxylic acid

Product 1

HCID 26596883(4S)-1-(tert-Butoxycarbonyl)-4-methyl-L-proline

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution of (S)-1-(tert-butoxycarbonyl)-4-methylenepyrrolidine-2-carboxylic acid Example M.4b (4 g, 17.60 mmol) in 2-propanol (10 mL) was added to a nitrogen purged suspension of 10% palladium on carbon (936 mg) in 2-propanol (240 mL) and the flask was charged with hydrogen gas (1 atm). After being stirred 18, the catalyst was removed by filtration over celite and the filtrate concentrated. LC analysis showed the sample contained ˜14% of the trans isomer, and recrystallization from toluene enriched the cis isomer, Example M.4c, to 96% purity (16:1). 1H NMR (500 MHz, MeOD) δ ppm 4.21-4.17 (m, 1H), 3.76-3.67 (m, 1H), 2.96-2.92 (m, 1H), 2.49-2.46 (m, 1H), 2.30-2.29 (m, 1H), 1.59-1.51 (m, 1H), 1.47/1.43 (m, 9H), 1.10-1.06 (m, 3H).

Workup

  1. custompurged
  2. additionsuspension of 10% palladium on carbon (936 mg) in 2-propanol (240 mL)
  3. additionthe flask was charged with hydrogen gas (1 atm)
  4. customthe catalyst was removed by filtration over celite
  5. concentrationthe filtrate concentrated
  6. custom˜14% of the trans isomer, and recrystallization from toluene

Sources & evidence

ORD record
ord-452e6741b31d4dfd80458f6169407a56
Source dataset
uspto-grants-2013_03
Patent number
US08394968B2

Reaction notes

Loading…