Cesium carbonate → [(methoxy{[(3S,3aS,6R,6aS)-6-(nitrooxy)hexahydrofuro[3,2-b]furan-3-yl]oxy}phosphoryl)oxy]methyl 2-butyl-4-chloro-1-{[2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazole-5-carboxylate

HRID 384580Notes

Reaction equation

HRID 384580 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[P:7]([O:14][C@H:15]1[CH2:19][O:18][C@@H:17]2[C@H:20]([O:23][N+:24]([O-:26])=[O:25])[CH2:21][O:22][C@H:16]12)([O:12][CH3:13])([O:9][CH2:10]Cl)=[O:8].[CH2:27]([C:31]1[N:32]([CH2:40][C:41]2[CH:46]=[CH:45][C:44]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][C:48]=3[C:53]3[N:57]([C:58]([C:71]4[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=4)([C:65]4[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=4)[C:59]4[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=4)[N:56]=[N:55][N:54]=3)=[CH:43][CH:42]=2)[C:33]([C:37]([OH:39])=[O:38])=[C:34]([Cl:36])[N:35]=1)[CH2:28][CH2:29][CH3:30]>CN(C)C=O>[CH2:27]([C:31]1[N:32]([CH2:40][C:41]2[CH:42]=[CH:43][C:44]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][C:48]=3[C:53]3[N:57]([C:58]([C:59]4[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=4)([C:71]4[CH:72]=[CH:73][CH:74]=[CH:75][CH:76]=4)[C:65]4[CH:66]=[CH:67][CH:68]=[CH:69][CH:70]=4)[N:56]=[N:55][N:54]=3)=[CH:45][CH:46]=2)[C:33]([C:37]([O:39][CH2:10][O:9][P:7]([O:12][CH3:13])([O:14][C@H:15]2[CH2:19][O:18][C@@H:17]3[C@H:20]([O:23][N+:24]([O-:26])=[O:25])[CH2:21][O:22][C@H:16]23)=[O:8])=[O:38])=[C:34]([Cl:36])[N:35]=1)[CH2:28][CH2:29][CH3:30]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 467832052-Butyl-4-chloro-1-({2'-[1-(triphenylmethyl)-1H-tetrazol-5-yl][1,1'-biphenyl]-4-yl}methyl)-1H-imidazole-5-carboxylic acid2×HCID 86652100chloromethyl methyl (3S,3aS,6R,6aS)-6-(nitrooxy)hexahydrofuro[3,2-b]furan-3-yl phosphate

Product 1

HCID 86652101[(methoxy{[(3S,3aS,6R,6aS)-6-(nitrooxy)hexahydrofuro[3,2-b]furan-3-yl]oxy}phosphoryl)oxy]methyl 2-butyl-4-chloro-1-{[2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazole-5-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Cesium carbonate (29.3 mg, 0,090 mmol) was added to a stirred, room temperature mixture of chloromethyl methyl (3S,3aS,6R,6aS)-6-(nitrooxy)hexahydrofuro[3,2-b]furan-3-yl phosphate (30 mg, 0.090 mmol) and 2-butyl-4-chloro-1-{[2′-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazole-5-carboxylic acid (Intermediate 4, 61.1 mg, 0.090 mmol) in N,N-dimethylformamide and the mixture was stirred at room temperature for overnight. The reaction was cooled, quenched with water and extracted with ethyl acetate. The organic phase was washed with saturated brine, dried (sodium sulfate), filtered and concentrated in vacua. Chromatography over silica, eluting with 40-100% ethyl acetate/hexane afforded the separated diastereomers.

Workup

  1. temperatureThe reaction was cooled
  2. customquenched with water
  3. extractionextracted with ethyl acetate
  4. washThe organic phase was washed with saturated brine
  5. dry with materialdried (sodium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated in vacua
  8. washChromatography over silica, eluting with 40-100% ethyl acetate/hexane
  9. customafforded the separated diastereomers

Sources & evidence

ORD record
ord-915be2156cd94baabd02ec177d9a4139
Source dataset
uspto-grants-2013_02
Patent number
US08367711B2

Reaction notes

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