Sodium Bicarbonate → HCID 58557891, compound

HRID 1969531Notes

Reaction equation

HRID 1969531 reaction equation
[N:1]([C@@H:4]1[CH2:8][N:7]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C@H:6]([CH3:16])[CH2:5]1)=[N+]=[N-].[CH:17]1([S:20](Cl)(=[O:22])=[O:21])[CH2:19][CH2:18]1.C([O-])(O)=O.[Na+]>CCO.[OH-].[OH-].[Pd+2]>[CH:17]1([S:20]([NH:1][C@@H:4]2[CH2:8][N:7]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C@H:6]([CH3:16])[CH2:5]2)(=[O:22])=[O:21])[CH2:19][CH2:18]1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 2760919Cyclopropanesulfonyl chlorideHCID 140411971,1-Dimethylethyl (2R,4S)-4-azido-2-methyl-1-pyrrolidinecarboxylate

Product 1

HCID 58557891HCID 58557891, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolvent2×

Procedure

To a slurry of 20 wt % Pd(OH)2 on C (0.605 g, 0.862 mmol) in EtOH (75 mL) was added a solution of (2R,4S)-tert-butyl 4-azido-2-methylpyrrolidine-1-carboxylate (3.9 g, 17 mmol, synthesized as described in Rosen, T.; Chu, D. T. W.; Lico, I. M.; Fernandes, P. B.; Marsh, K.; Shen, L.; Cepa, V. G.; Pernet, A. G. J. Med. Chem. 1988, 31, 1598-1611) in EtOH (25 mL). The reaction mixture was sparged with hydrogen and an atmosphere of hydrogen was maintained via balloon. The reaction mixture was stirred for about 2 h at ambient temperature and then was filtered and concd in vacuo. The residue was dissolved in DCM (100 mL), cooled to about 0° C. and TEA (6.01 mL, 43.1 mmol) was added followed by cyclopropanesulfonyl chloride (2.67 g, 19.0 mmol). The reaction mixture was stirred at ambient temperature for about 15 h, saturated aqueous NaHCO3 (50 mL) was added to the reaction mixture and the organic layer was separated, concd in vacuo, and purified by chromatography on silica gel (80 g) eluting with 20-80% EtOAc in heptane to provide (2R,4S)-tert-butyl 4-(cyclopropanesulfonamido)-2-methylpyrrolidine-1-carboxylate (2.55 g, 48%) as an oil: LC/MS (Table 1, Method a) Rt=1.98 min (ELSD); MS m/z: 305 (M+H)+.

Workup

  1. customsynthesized
  2. customThe reaction mixture was sparged with hydrogen
  3. temperaturean atmosphere of hydrogen was maintained via balloon
  4. filtrationwas filtered
  5. dissolutionThe residue was dissolved in DCM (100 mL)
  6. temperaturecooled to about 0° C.
  7. stirringThe reaction mixture was stirred at ambient temperature for about 15 h
  8. customthe organic layer was separated
  9. customconcd in vacuo, and purified by chromatography on silica gel (80 g)
  10. washeluting with 20-80% EtOAc in heptane

Sources & evidence

ORD record
ord-49c8b6fcdac1441ab3e13aab4df9c238
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

Loading…