Cyclopropanesulfonyl chloride → HCID 58557752, compound

HRID 1969532Notes

Reaction equation

HRID 1969532 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]([CH2:16][CH3:17])[CH2:5]1)=[N+]=[N-].[CH:18]1([S:21](Cl)(=[O:23])=[O:22])[CH2:20][CH2:19]1>CCO.[OH-].[OH-].[Pd+2]>[CH:18]1([S:21]([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]([CH2:16][CH3:17])[CH2:5]2)(=[O:23])=[O:22])[CH2:20][CH2:19]1

Participants

5

Reactant 2

HCID 2760919Cyclopropanesulfonyl chlorideHCID 86660431HCID 86660431, compound

Product 1

HCID 58557752HCID 58557752, compoundYield 48%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolvent2×

Procedure

To a slurry of 20 wt % Pd(OH)2 on C (0.044 g, 0.062 mmol) in EtOH (30 mL) was added a solution of (2R,4S)-tert-butyl 4-azido-2-ethylpyrrolidine-1-carboxylate (1.5 g, 6.2 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 (10 mL). The reaction mixture was sparged with hydrogen and an atmosphere of hydrogen was maintained via balloon. The reaction mixture was stirred for about 4 h at ambient temperature and then was filtered and concd in vacuo. The residue was dissolved in pyridine (30 mL) and cyclopropanesulfonyl chloride (1.05 g, 7.49 mmol) was added. The reaction mixture was stirred for about 15 h at ambient temperature and then was partitioned between EtOAc (50 mL) and saturated aqueous CuSO4 (50 mL). The organic layer was separated, washed with brine (30 mL), dried over anhydrous Na2SO4, filtered, 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-ethylpyrrolidine-1-carboxylate (0.95 g, 48%) as an oil: LC/MS (Table 1, Method a) Rt=2.12 min (ELSD); MS m/z: 319 (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 pyridine (30 mL)
  6. stirringThe reaction mixture was stirred for about 15 h at ambient temperature
  7. customwas partitioned between EtOAc (50 mL) and saturated aqueous CuSO4 (50 mL)
  8. customThe organic layer was separated
  9. washwashed with brine (30 mL)
  10. dry with materialdried over anhydrous Na2SO4
  11. filtrationfiltered
  12. customconcd in vacuo, and purified by chromatography on silica gel (80 g)
  13. washeluting with 20-80% EtOAc in heptane

Sources & evidence

ORD record
ord-b16dcf5363ec4c7ba1416df660170df5
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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