Sodium hydride → tert-butyl 3-((1S,2S,5R)-2-(benzyloxycarbonylamino)-5-(tert-butoxycarbonylamino)cyclohexyl)acrylate

HRID 2225260Notes

Reaction equation

HRID 2225260 reaction equation
[H-].[Na+].COP([CH2:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])(OC)=O.[CH2:17]([O:24][C:25]([NH:27][C@H:28]1[CH2:34][CH2:33][C@@H:32]2[CH2:35][C@H:29]1[CH:30](O)[N:31]2[C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])=[O:26])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[NH4+].[Cl-]>O1CCCC1.C(OCC)(=O)C>[CH2:17]([O:24][C:25]([NH:27][C@H:28]1[CH2:34][CH2:33][C@@H:32]([NH:31][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:35][C@H:29]1[CH:30]=[CH:9][C:10]([O:12][C:13]([CH3:14])([CH3:15])[CH3:16])=[O:11])=[O:26])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 4564495tert-Butyl DimethylphosphonoacetateHCID 69284642(1R,2S,5R)-tert-butyl 2-(benzyloxycarbonylamino)-7-hydroxy-6-aza-bicyclo[3.2.1]octane-6-carboxylate

Product 1

HCID 69287227tert-butyl 3-((1S,2S,5R)-2-(benzyloxycarbonylamino)-5-(tert-butoxycarbonylamino)cyclohexyl)acrylate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A stirred suspension of NaH (60% in mineral oil, 160 mg) in tetrahydrofuran (3 mL) on an ice bath was treated dropwise over 10 min with tert-butyl dimethylphosphonoacetate (0.796 mL). The mixture was stirred at rt for 15 min, then was cooled again on an ice bath and treated with a solution of (1R,2S,5R)-tert-butyl 2-(benzyloxycarbonylamino)-7-hydroxy-6-aza-bicyclo[3.2.1]octane-6-carboxylate (432 mg) in tetrahydrofuran (3 mL). The mixture was stirred at rt for 3 h. The mixture was treated with saturated aqueous NH4Cl and diluted with ethyl acetate. The phases were separated and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over Na2SO4 and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel, eluting with hexane/ethyl acetate to provide tert-butyl 3-((1S,2S,5R)-2-(benzyloxycarbonylamino)-5-(tert-butoxycarbonylamino)cyclohexyl)acrylate as a white glassy foam (308 mg). MS found: (M+H)+=475.5.

Workup

  1. temperaturewas cooled again on an ice bath
  2. stirringThe mixture was stirred at rt for 3 h
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted three times with ethyl acetate
  5. dry with materialThe combined organic phases were dried over Na2SO4
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by flash column chromatography on silica gel
  8. washeluting with hexane/ethyl acetate

Sources & evidence

ORD record
ord-ed3aff54a1044c0db8a7f141654bf778
Source dataset
uspto-grants-2008_05
Patent number
US07378409B2

Reaction notes

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