Methanol → HCID 70324238, compound

HRID 1423346Notes

Reaction equation

HRID 1423346 reaction equation
CO.[CH:3]1([S:6]([NH:9][C:10]([C@@:12]2([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:14][C@H:13]2[CH:15]=[CH2:16])=[O:11])(=[O:8])=[O:7])[CH2:5][CH2:4]1.CCCCCCC>CCOC(C)=O.[Ru]>[CH:3]1([S:6]([NH:9][C:10]([C@@:12]2([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:14][C@H:13]2[CH2:15][CH3:16])=[O:11])(=[O:8])=[O:7])[CH2:5][CH2:4]1

Participants

6

Reactant 3

HCID 887MethanolHCID 8900Heptane3×HCID 45480526Carbamic acid, N-[(1R,2S)-1-[[(cyclopropylsulfonyl)amino]carbonyl]-2-ethenylcyclopropyl]-, 1,1-dimethylethyl ester

Product 1

HCID 70324238HCID 70324238, compoundYield 75.7%

Reagents, catalysts & solvents 2

HCID 23950RutheniumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

A hydrogenaton vessel was charged with a methanol (1000 mL) slurry of tert-butyl ((1R,2S)-1-{[(cyclopropylsulfonyl)amino]carbonyl}-2-vinylcyclopropyl)carbamate (164 g, 0.50 mol) and 5% Ru/C (dry, 7.5 wt %, 12.4 g) and stirred. The vessel was placed under nitrogen (20 psig) and vented to atmospheric pressure three times to remove residual oxygen. The vessel was then placed under hydrogen (50 psig). After 20 h, the vessel was vented to atmospheric pressure. The reaction slurry was then transferred out of the reaction and filtered through SOLKA FLOK (34 grams, wetted w/100 mL MeOH) to yield a clear, light brown solution. The SOLKA FLOK was rinsed with MeOH (200 mL×2). The combined methanol solutions were concentrated under reduced pressure to yield crude product as a white solid (153 g). The crude product was slurried in EtOAc (800 mL), warmed to 40° C. and aged 30 min. The solution was then seeded, aged 30 min, and heptane (500 mL) was added via addition funnel over 30 min. The partially crystallized solid was cooled to RT and aged overnight after which additional heptane (500 mL) was added. After 1 h, additional heptane (250 mL) was added via addition funnel, and the white slurry aged for 1 h. The solution was filtered and the solid was rinsed with heptane/EtOAc (500 mL, 4:1) and dried under reduced pressure to give tert-butyl ((1R,2R)-1-{[(cyclopropylsulfonyl)amino]carbonyl}-2-ethylcyclopropyl)carbamate (125.9 g).

Workup

  1. customto remove residual oxygen
  2. customThe reaction slurry was then transferred out of the reaction
  3. filtrationfiltered through SOLKA FLOK (34 grams, wetted w/100 mL MeOH)
  4. customto yield a clear, light brown solution
  5. washThe SOLKA FLOK was rinsed with MeOH (200 mL×2)
  6. concentrationThe combined methanol solutions were concentrated under reduced pressure
  7. customto yield crude product as a white solid (153 g)
  8. waitaged 30 min
  9. additionwas added
  10. waitAfter 1 h
  11. waitthe white slurry aged for 1 h
  12. filtrationThe solution was filtered
  13. washthe solid was rinsed with heptane/EtOAc (500 mL, 4:1)
  14. customdried under reduced pressure

Sources & evidence

ORD record
ord-663264e0e0ae4c0a954bd4b02b16126c
Source dataset
uspto-grants-2015_01
Patent number
US08927569B2

Reaction notes

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