Hydrochloric Acid → (6S)-4-Nitrobenzyl 3-hydroxy-8-oxo-7-(N-phenylacetamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 1155824Notes

Reaction equation

HRID 1155824 reaction equation
[CH2:1]([C:8]1[S:14][CH:13]2[CH:10]([C:11](=[O:32])[N:12]2[C:15](=[C:29]([OH:31])[CH3:30])[C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=2)=[O:17])[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CS(Cl)(=O)=[O:35].N1CCOCC1.BrBr.Cl>O1CCCC1.CO.N1C=CC=CC=1.C(N(CC)CC)C>[C:2]1([CH2:1][C:8]([NH:9][CH:10]2[C:11](=[O:32])[N:12]3[C:15]([C:16]([O:18][CH2:19][C:20]4[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=4)=[O:17])=[C:29]([OH:31])[CH2:30][S:14][C@H:13]23)=[O:35])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 8083MorpholineHCID 24408BromineHCID 31297Methanesulfonyl chlorideHCID 70503680p-Nitrobenzyl alpha-(3-benzyl-7-oxo-4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl)-alpha-(1-hydroxyethylidene)acetate

Product 1

HCID 67685788(6S)-4-Nitrobenzyl 3-hydroxy-8-oxo-7-(N-phenylacetamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 71%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 1049PyridineSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

One adds triethylamine (5.68 ml) to a stirred suspension of p-nitrobenzyl α-[3-benzyl-7-oxo-4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl]-α-(1-hydroxyethylidene)acetate (9.06 g) in tetrahydrofuran (120 ml) under nitrogen atmosphere at -20° C. to give clear solution, adds methanesulfonyl chloride (1.65 ml) to the solution, stirs for 30 minutes at the same temperature, adds morpholine (1.92 ml), warms to 0° C., stirs for 5 hours, cools to -30° C. to -35° C., adds pyridine (1.54 ml) and bromine (3.12 g), stirs for 20 minutes, warms to ice-water temperature, adds 5% hydrochloric acid (144 ml) and methanol (120 ml), stirs for 3 hours at room temperature, and lets stand overnight at 0° C. Collection of the separated crystals in the reaction mixture by filtration gives p-nitrobenzyl 7-phenylacetamido-3-hydroxy-3-cephem-4-carboxylate (6.678 g). m.p. 201° C. Yield: 71%.

Workup

  1. customto give clear solution
  2. customwarms to 0° C.
  3. waitstirs for 20 minutes
  4. waitstirs for 3 hours at room temperature
  5. waitlets stand overnight at 0° C
  6. customCollection of the separated crystals in the reaction mixture
  7. filtrationby filtration

Sources & evidence

ORD record
ord-6fc74df76ec8431e9351bf7756f3241c
Source dataset
uspto-grants-1982_06
Patent number
US04332722

Reaction notes

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