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

HRID 625648Notes

Reaction equation

HRID 625648 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 (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 to 96% (16:1). LC-MS retention time 3.26 min; calcd. for C11H20N6O4: 230.14 m/z Found 252.14 [M+Na]+. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a PHENOMENEX® 2×5 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 0.8 mL/min, a gradient of 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B, a gradient time of 4 min, a hold time of 1 min and an analysis time of 5 min where Solvent A was 10% methanol/90% water/0.1% TFA and Solvent B was 90% methanol/10% water/0.1% TFA. MS data was determined using a MICROMASS® Platform for LC in electrospray mode. 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
  7. customequipped with a PHENOMENEX® 2×5 mm column
  8. washThe elution conditions
  9. customa gradient time of 4 min
  10. customa hold time of 1 min
  11. customan analysis time of 5 min where Solvent A was 10% methanol/90% water/0.1% TFA and Solvent B

Sources & evidence

ORD record
ord-0adc9a6c524b493da14331ad07cbfc53
Source dataset
uspto-grants-2016_04
Patent number
US09303007B2

Reaction notes

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