Methanol → HCID 70324238, compound

HRID 2045689Notes

Reaction equation

HRID 2045689 reaction equation
CO.[C:3]([O:7][C:8](=[O:24])[NH:9][C@:10]1([C:15]([NH:17][S:18]([CH:21]2[CH2:23][CH2:22]2)(=[O:20])=[O:19])=[O:16])[CH2:12][C@H:11]1[CH:13]=[CH2:14])([CH3:6])([CH3:5])[CH3:4].CCCCCCC>CCOC(C)=O.[Ru]>[C:3]([O:7][C:8](=[O:24])[NH:9][C@:10]1([C:15]([NH:17][S:18]([CH:21]2[CH2:22][CH2:23]2)(=[O:20])=[O:19])=[O:16])[CH2:12][C@H:11]1[CH2:13][CH3:14])([CH3:4])([CH3:5])[CH3:6]

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 hydrogenation vessel was charged with a MeOH (1000 mL) slurry of tert-butyl((1R,2S)-1-{[(cyclopropylsulfonyl)amino]carbonyl}-2-vinylcyclopropyl)carbamate (164 g, 0.50 mol) (U.S. Pat. No. 6,995,174) and 5% Ru/C (dry, 7.5 wt %, 12.4 g) and set stirring. 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 with 100 mL MeOH) to yield a clear, light brown solution. The SOLKA FLOK was rinsed with MeOH (200 mL×2). The combined MeOH 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 for 30 min. The solution was then seeded, aged for 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 with 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 MeOH solutions were concentrated under reduced pressure
  7. customto yield crude product as a white solid (153 g)
  8. waitaged for 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-49ce7b3992b04901bb50439eb7103dec
Source dataset
uspto-grants-2013_11
Patent number
US08591878B2

Reaction notes

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