Diphenyl chlorophosphate → 4-nitrobenzyl(5R,6S)-6-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-3-[2-(4-nitrobenzyloxycarbonylamino)-ethylthio]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate

HRID 1719331Notes

Reaction equation

HRID 1719331 reaction equation
O=[C:2]1[CH2:8][C@H:7]2[N:4]([C:5](=[O:26])[C@@H:6]2[C:9]([CH3:25])([O:11][C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=2)=[O:13])[CH3:10])[C@H:3]1[C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][C:34]([N+:37]([O-:39])=[O:38])=[CH:33][CH:32]=1)=[O:28].C(N(C(C)C)CC)(C)C.P(Cl)(OC1C=CC=CC=1)(OC1C=CC=CC=1)=O.[N+:66]([C:69]1[CH:82]=[CH:81][C:72]([CH2:73][O:74][C:75]([NH:77][CH2:78][CH2:79][SH:80])=[O:76])=[CH:71][CH:70]=1)([O-:68])=[O:67]>C(#N)C.C(OCC)(=O)C>[CH3:25][C:9]([C@H:6]1[C:5](=[O:26])[N:4]2[C@@H:7]1[CH2:8][C:2]([S:80][CH2:79][CH2:78][NH:77][C:75]([O:74][CH2:73][C:72]1[CH:81]=[CH:82][C:69]([N+:66]([O-:68])=[O:67])=[CH:70][CH:71]=1)=[O:76])=[C:3]2[C:27]([O:29][CH2:30][C:31]1[CH:32]=[CH:33][C:34]([N+:37]([O-:39])=[O:38])=[CH:35][CH:36]=1)=[O:28])([O:11][C:12]([O:14][CH2:15][C:16]1[CH:17]=[CH:18][C:19]([N+:22]([O-:24])=[O:23])=[CH:20][CH:21]=1)=[O:13])[CH3:10]

Participants

7

Reactant 4

HCID 75654Diphenyl chlorophosphateHCID 81531Diisopropylethylamine2×HCID 3017625(4-Nitrophenyl)methyl (2-mercaptoethyl)carbamateHCID 228231934-nitrobenzyl(2R,5R,6S)-3,7-dioxo-6-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-1-azabicyclo[3.2.0]heptane-2-carboxylate

Product 1

HCID 185992134-nitrobenzyl(5R,6S)-6-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-3-[2-(4-nitrobenzyloxycarbonylamino)-ethylthio]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylateYield 78.5%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent5×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-nitrobenzyl(2R,5R,6S)-3,7-dioxo-6-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-1-azabicyclo[3.2.0]heptane-2-carboxylate (148.5 mg) and 4-N,N-dimethylaminopyridine (3.35 mg) in acetonitrile (7.4 ml) was added dropwise a solution of di-isopropylethylamine (57.3 μl) in acetonitrile (0.516 ml). To the mixture was further added a solution of diphenyl chlorophosphate (59.6 μl) in acetonitrile (0.536 ml) at 0° C. After stirring for an hour at 0° C., a solution of diisopropylethylamine (190.9 μl) in acetonitrile (1.72 ml) was added to the mixture. To the mixture was further added a solution of N-(4-nitrobenzyloxycarbonyl)cysteamine (73.8 mg) in acetonitrile (0.664 ml) at -15° C. The mixture was allowed to stand overnight at -15° C. The resulting solution was diluted with ethyl acetate (15 ml) and washed in turn with water and saturated aqueous sodium chloride. After drying over magnesium sulfate, the ethyl acetate extract was filtered and evaporated in vacuo. The residue was chromatographed on silica gel (3 g) eluting with a mixture of methylene chloride and ethyl acetate (50:1 to 5:1) to give 4-nitrobenzyl(5R,6S)-6-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-3-[2-(4-nitrobenzyloxycarbonylamino)-ethylthio]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (167.8 mg) as an amorphous solid.

Workup

  1. washwashed in turn with water and saturated aqueous sodium chloride
  2. dry with materialAfter drying over magnesium sulfate
  3. extractionthe ethyl acetate extract
  4. filtrationwas filtered
  5. customevaporated in vacuo
  6. customThe residue was chromatographed on silica gel (3 g)
  7. washeluting with a mixture of methylene chloride and ethyl acetate (50:1 to 5:1)

Sources & evidence

ORD record
ord-2cf227843a1447caaef5b5b6b896b4ae
Source dataset
uspto-grants-1985_09
Patent number
US04539152

Reaction notes

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