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

HRID 235762Notes

Reaction equation

HRID 235762 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.C1(OP(Cl)(OC2C=CC=CC=2)=O)C=CC=CC=1.[SH:66][C:67]1[CH:72]=[CH:71][N:70]=[CH:69][CH:68]=1>CN(C1C=CN=CC=1)C.C(#N)C.C(OCC)(=O)C>[N:70]1[CH:71]=[CH:72][C:67]([S:66][C:2]2[CH2:8][C@H:7]3[N:4]([C:5](=[O:26])[C@@H:6]3[C:9]([CH3:25])([O:11][C:12]([O:14][CH2:15][C:16]3[CH:17]=[CH:18][C:19]([N+:22]([O-:24])=[O:23])=[CH:20][CH:21]=3)=[O:13])[CH3:10])[C:3]=2[C:27]([O:29][CH2:30][C:31]2[CH:32]=[CH:33][C:34]([N+:37]([O-:39])=[O:38])=[CH:35][CH:36]=2)=[O:28])=[CH:68][CH:69]=1

Participants

8

Reactant 4

HCID 75654Diphenyl chlorophosphateHCID 81531Diisopropylethylamine2×HCID 228231934-nitrobenzyl(2R,5R,6S)-3,7-dioxo-6-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-1-azabicyclo[3.2.0]heptane-2-carboxylateHCID 178418431pyridine-4-thiol

Product 1

HCID 186065884-nitrobenzyl(5R,6S)-3-(4-pyridylthio)-6-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylateYield 81.8%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent4×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 (145.1 mg) and 4-(N,N-dimethylamino)pyridine (3.27 mg) in acetonitrile (7.3 ml) was added dropwise a solution of N,N-diisopropyl-N-ethylamine (56.0 μl) in acetonitrile (0.504 μl), followed by a solution of diphenyl-chlorophosphate (58.3 μl) in acetonitrile (0.525 ml) at 0° C. After stirring for an hour at 0° C., thereto was added a solution of N,N-diisopropyl-N-ethylamine (186.4 μl) in acetonitrile (1.68 ml), followed by 4-mercaptopyridine (31.3 mg) at -15° C. The mixture was allowed to stand overnight at -15° C. The resultant solution was diluted with ethyl acetate (15 ml) and then washed in turn with water and saturated aqueous sodium chloride. After drying over magnesium sulfate, the solution was filtered and evaporated in vacuo. The residue was chromatographed on silica gel (4 g) eluting with a mixture of benzene and acetone (30:1 to 6:1) to give 4-nitrobenzyl(5R,6S)-3-(4-pyridylthio)-6-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (139.1 mg).

Workup

  1. washwashed in turn with water and saturated aqueous sodium chloride
  2. dry with materialAfter drying over magnesium sulfate
  3. filtrationthe solution was filtered
  4. customevaporated in vacuo
  5. customThe residue was chromatographed on silica gel (4 g)
  6. washeluting with a mixture of benzene and acetone (30:1 to 6:1)

Sources & evidence

ORD record
ord-fd9f3682bbc5487bbca0457adf4f9b00
Source dataset
uspto-grants-1987_02
Patent number
US04640915

Reaction notes

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