Ammonium Chloride → methyl 3-((E)-2-((1S,2S,5R)-2-benzyloxycarbonylamino-5-(tert-butoxycarbonylamino)cyclohexyl)vinyl)benzoate

HRID 2225263Notes

Reaction equation

HRID 2225263 reaction equation
[Br-].[CH3:2][O:3][C:4]([C:6]1[CH:7]=[C:8]([CH:29]=[CH:30][CH:31]=1)[CH2:9][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)=[O:5].C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH2:42]([O:49][C:50]([NH:52][C@H:53]1[CH2:59][CH2:58][C@@H:57]2[CH2:60][C@H:54]1[CH:55](O)[N:56]2[C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])=[O:51])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.[NH4+].[Cl-]>O1CCCC1>[CH2:42]([O:49][C:50]([NH:52][C@H:53]1[CH2:59][CH2:58][C@@H:57]([NH:56][C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[CH2:60][C@H:54]1/[CH:55]=[CH:9]/[C:8]1[CH:7]=[C:6]([CH:31]=[CH:30][CH:29]=1)[C:4]([O:3][CH3:2])=[O:5])=[O:51])[C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 10051285Phosphonium, [[3-(methoxycarbonyl)phenyl]methyl]triphenyl-, bromideHCID 69284642(1R,2S,5R)-tert-butyl 2-(benzyloxycarbonylamino)-7-hydroxy-6-aza-bicyclo[3.2.1]octane-6-carboxylate

Product 1

HCID 69286602methyl 3-((E)-2-((1S,2S,5R)-2-benzyloxycarbonylamino-5-(tert-butoxycarbonylamino)cyclohexyl)vinyl)benzoateYield 58.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of 3-(methoxycarbonyl)benzyltriphenylphosphonium bromide (1.8 g, see J. Chem. Soc. 1961, 5015) in tetrahydrofuran (5 mL) was stirred on an ice bath and treated dropwise over 10 min with a solution of potassium bis(trimethylsilyl)amide (0.5 M in toluene, 7.3 mL). The resulting yellow suspension was stirred on ice for 15 min, then was treated with a solution of (1R,2S,5R)-tert-butyl 2-(benzyloxycarbonylamino)-7-hydroxy-6-aza-bicyclo[3.2.1]octane-6-carboxylate (460 mg) in tetrahydrofuran (3 mL). After allowing to stir on an ice bath for 75 min, the mixture was stirred at rt for 3 h. Saturated aqueous NH4Cl was added, the mixture was stirred rapidly until colorless, then was extracted three times with ethyl acetate. The combined organic phases were washed with 1.0 M aqueous HCl, then with brine, dried over Na2SO4 and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel, eluting with 2:1 v/v hexane-ethyl acetate, to provide methyl 3-((E)-2-((1S,2S,5R)-2-benzyloxycarbonylamino-5-(tert-butoxycarbonylamino)cyclohexyl)vinyl)benzoate as a glassy foam (365 mg). MS found: (M+H)+=509.3.

Workup

  1. stirringThe resulting yellow suspension was stirred on ice for 15 min
  2. stirringto stir on an ice bath for 75 min
  3. stirringthe mixture was stirred at rt for 3 h
  4. stirringthe mixture was stirred rapidly until colorless,
  5. extractionthen was extracted three times with ethyl acetate
  6. washThe combined organic phases were washed with 1.0 M aqueous HCl
  7. dry with materialwith brine, dried over Na2SO4
  8. concentrationconcentrated under vacuum
  9. customThe residue was purified by flash column chromatography on silica gel
  10. washeluting with 2:1 v/v hexane-ethyl acetate

Sources & evidence

ORD record
ord-29a784bd4d6c4a4ea62f7ed496004446
Source dataset
uspto-grants-2008_05
Patent number
US07378409B2

Reaction notes

Loading…