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

HRID 235770Notes

Reaction equation

HRID 235770 reaction equation
O=[C:2]1[CH2:8][C@H:7]2[N:4]([C:5](=[O:14])[C@@H:6]2[C:9]([O:12][CH3:13])([CH3:11])[CH3:10])[C@H:3]1[C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][CH:20]=1)=[O:16].C(N(C(C)C)CC)(C)C.P(Cl)(OC1C=CC=CC=1)(OC1C=CC=CC=1)=O.[N:54]1[CH:59]=[CH:58][C:57]([SH:60])=[CH:56][CH:55]=1>CN(C1C=CN=CC=1)C.C(#N)C>[CH3:13][O:12][C:9]([C@H:6]1[C:5](=[O:14])[N:4]2[C@@H:7]1[CH2:8][C:2]([S:60][C:57]1[CH:58]=[CH:59][N:54]=[CH:55][CH:56]=1)=[C:3]2[C:15]([O:17][CH2:18][C:19]1[CH:20]=[CH:21][C:22]([N+:25]([O-:27])=[O:26])=[CH:23][CH:24]=1)=[O:16])([CH3:11])[CH3:10]

Participants

7

Reactant 4

HCID 75654Diphenyl chlorophosphateHCID 81531Diisopropylethylamine2×HCID 867412824-nitrobenzyl (2R, 5R, 6S)-3,7-dioxo-6-(1-methoxy-1-methylethyl)-1-azabicyclo[3.2.0]-heptane-2-carboxylateHCID 178418431pyridine-4-thiol

Product 1

HCID 572670844-nitrobenzyl (5R, 6S)-6-(1-methoxy-1-methylethyl)-7-oxo-3-(4-pyridylthio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylateYield 82.9%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent4×

Conditions

Temperature
0 °C

Procedure

To a solution of 4-nitrobenzyl (2R, 5R, 6S)-3,7-dioxo-6-(1-methoxy-1-methylethyl)-1-azabicyclo[3.2.0]heptane-2-carboxylate (50.0 mg) and 4-(N,N-dimethylamino)pyridine (1.62 mg) in acetonitrile (2.5 ml) was added dropwise a solution of N,N-diisopropyl-N-ethylamine (27.8 μl) in acetonitrile (0.25 ml), followed by addition of a solution of diphenyl chlorophosphate (28.9 μl) in acetonitrile (0.26 ml) at 0° C. After stirring for one hour at 0° C., a solution of N,N-diisopropyl-N-ethylamine (92.7 μl) in acetonitrile (0.834 ml) and pyridine-4-thiol (15.6 mg) were successively added at -15° C., and the mixture was allowed to stand at -15° C. overnight. The resultant solution was concentrated in vacuo. The residue was diluted with ethyl acetate (10 ml) and washed twice with water and a saturated aqueous sodium chloride. After drying over magnesium sulfate, the ethyl acetate solution was filtered and evaporated. The residue (68.7 mg) was chromatographed on deactivated silica gel (1.5 g) with 10% water, eluting with a mixture of benzene and acetone (100:1 to 6:1) to give 4-nitrobenzyl (5R, 6S)-6-(1-methoxy-1-methylethyl)-7-oxo-3-(4-pyridylthio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (51.7 mg) as an amorphous solid.

Workup

  1. waitto stand at -15° C. overnight
  2. concentrationThe resultant solution was concentrated in vacuo
  3. additionThe residue was diluted with ethyl acetate (10 ml)
  4. washwashed twice with water
  5. dry with materialAfter drying over magnesium sulfate
  6. filtrationthe ethyl acetate solution was filtered
  7. customevaporated
  8. customThe residue (68.7 mg) was chromatographed on deactivated silica gel (1.5 g) with 10% water
  9. washeluting with a mixture of benzene and acetone (100:1 to 6:1)

Sources & evidence

ORD record
ord-0839fae27b184232a433adaf9ebe4c56
Source dataset
uspto-grants-1987_02
Patent number
US04640915

Reaction notes

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