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

HRID 851423Notes

Reaction equation

HRID 851423 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.[SH:66][CH2:67][CH2:68][NH:69][C:70](=[O:72])[CH3:71]>CN(C1C=CN=CC=1)C.C(#N)C.C(OCC)(=O)C>[C:70]([NH:69][CH2:68][CH2:67][S:66][C:2]1[CH2:8][C@H:7]2[N:4]([C:5](=[O:26])[C@@H:6]2[C:9]([CH3:10])([O:11][C:12]([O:14][CH2:15][C:16]2[CH:17]=[CH:18][C:19]([N+:22]([O-:24])=[O:23])=[CH:20][CH:21]=2)=[O:13])[CH3:25])[C:3]=1[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:72])[CH3:71]

Participants

8

Reactant 4

HCID 14484AcetylcysteamineHCID 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-carboxylate

Product 1

HCID 228231944-nitrobenzyl (5R,6S)-3-(2-acetamidoethylthio)-6-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylateYield 95.2%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 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 (47.8 mg) and 4-(N,N-dimethylamino)pyridine (1.08 mg) in acetonitrile (2.39 ml) was added dropwise a solution of di-isopropylethylamine (18.5 μl) in acetonitrile (166.5 μl) followed by addition of a solution of diphenyl chlorophosphate (19.2 μl) in acetonitrile (172.8 μl) at 0° C. After stirring for an hour at 0° C., a solution of di-isopropylethylamine (61.5 μl) in acetonitrile (553.5 μl) was added followed by addition of a solution of N-(2-mercaptoethyl)acetamide (11.05 mg) in acetonitrile (99.45 μl) at -15° C. The mixture was allowed to stand overnight at -15° C. The resulting solution was diluted with ethyl acetate (34 ml) and washed with dilute aqueous sodium chloride and saturated aqueous sodium chloride. After drying over magnesium sulfate, the ethyl acetate extract was filtered and evaporated in vacuo. The residual oil (76.4 mg) was chromatographed on silica gel (1.5 g) eluting with a mixture of methylene chloride and acetone (20:1 to 2:1) to give 4-nitrobenzyl(5R,6S)-3-(2-acetamido-ethylthio)-6-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylate (54.0 mg) as an amorphous solid.

Workup

  1. washwashed with dilute aqueous sodium chloride 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 residual oil (76.4 mg) was chromatographed on silica gel (1.5 g)
  7. washeluting with a mixture of methylene chloride and acetone (20:1 to 2:1)

Sources & evidence

ORD record
ord-6c7a99408b4c465c901c4c7c616b9365
Source dataset
uspto-grants-1983_05
Patent number
US04383945

Reaction notes

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