Diphenyl chlorophosphate → HCID 53907551, compound

HRID 1719336Notes

Reaction equation

HRID 1719336 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]>CN(C1C=CN=CC=1)C.C(#N)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 185992114-nitrobenzyl (2R,5R,6R)-3,7-dioxo-6-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-1-azabicyclo[3.2.0]heptane-2-carboxylate

Product 1

HCID 53907551HCID 53907551, compoundYield 82.6%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent4×

Conditions

Temperature
0 °C

Procedure

To a solution of 4-nitrobenzyl (2R,5R,6R)-3,7-dioxo-6-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-1-azabicyclo[3.2.0]heptane-2-carboxylate (602 mg) and 4-(N,N-dimethylamino)pyridine (13.6 ml) in acetonitrile (30 ml) was added a solution of diisopropylethylamine (0.232 ml) in acetonitrile (2.08 ml) at 0° C. To the mixture was further added a solution of diphenyl chlorophosphate (0.242 ml) in acetonitrile (2.18 ml). After stirring at 0° C. for an hour, the mixture was cooled to -15° C. To the mixture was added a solution of diisopropylethylamine (0.775 ml) in acetonitrile (6.97 ml) and N-(4-nitrobenzyloxycarbonyl)cysteamine (299 mg) were added. After standing overnight at -15° C., the mixture was evaporated in vacuo. The residue was dissolved in ethyl acetate (100 ml) and the solution was washed in turn with water and saturated aqueous sodium chloride, dried over magnesium sulfate, and evaporated in vacuo. The residue was chromatographed on silica gel (18 g) eluting with a mixture of benzene and acetone (20:1 to 6:1) to give 4-nitrobenzyl (5R,6R)-6-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-3-[2-(4-nitrobenzyloxycarbonylamino)ethylthio]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (716 mg) as an amorphous solid.

Workup

  1. temperaturethe mixture was cooled to -15° C
  2. additionwere added
  3. customthe mixture was evaporated in vacuo
  4. dissolutionThe residue was dissolved in ethyl acetate (100 ml)
  5. washthe solution was washed in turn with water and saturated aqueous sodium chloride
  6. dry with materialdried over magnesium sulfate
  7. customevaporated in vacuo
  8. customThe residue was chromatographed on silica gel (18 g)
  9. washeluting with a mixture of benzene and acetone (20:1 to 6:1)

Sources & evidence

ORD record
ord-06329608167e4a6782e1f7a994da94d6
Source dataset
uspto-grants-1985_09
Patent number
US04539152

Reaction notes

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