Tetrahydrofuran → Benzyl alpha-[3-phenoxymethyl-7-oxo4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl]-alpha-(methanesulfonyloxyethylidene)acetate

HRID 67855Notes

Reaction equation

C(N(CC)CC)C.[CH3:8][S:9](Cl)(=[O:11])=[O:10].[O:13]([CH2:20][C:21]1[S:27][CH:26]2[CH:23]([C:24](=[O:42])[N:25]2[C:28](=[C:39](O)[CH3:40])[C:29]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[O:30])[N:22]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[O:43]1CCCC1>>[O:13]([CH2:20][C:21]1[S:27][CH:26]2[CH:23]([C:24](=[O:42])[N:25]2[C:28](=[CH:39][CH2:40][O:10][S:9]([CH3:8])(=[O:11])=[O:43])[C:29]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[O:30])[N:22]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

Reactant 4

HCID 8028Tetrahydrofuran

HCID 8471Triethylamine

HCID 31297Methanesulfonyl chloride

HCID 70503985Benzyl alpha-[3-phenoxymethyl-7-oxo-4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl]-alpha-(1-hydroxyethylidene)acetate

Product 1

HCID 53869939Benzyl alpha-[3-phenoxymethyl-7-oxo4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl]-alpha-(methanesulfonyloxyethylidene)acetate

Procedure

One adds triethylamine (1.42 ml), and methanesulfonyl chloride (0.41 ml) to a solution of benzyl α-[3-phenoxymethyl-7-oxo-4-thia-2,6-diazabicyclo[3,2,0]hept-2en-6-yl]-α-(1-hydroxyethylidene)acetate (2.12 g) in tetrahydrofuran (30 ml) at -30° C., stirs for 70 minutes to give benzyl α-[3-phenoxymethyl-7-oxo-4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl]-α-(methanesulfonyloxyethylidene)acetate, adds morphline (0.6 ml) and stirs for 4 hours 50 minutes at 0° C. to give benzyl α-[3-phenoxymethyl-7-oxo-4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl]-α-(1-morpholinoethylidene)acetate, cools to -50° C., adds pyridine (0.385 ml) and bromine (0.25 ml), and stirs for 30 minutes to give benzyl α-[3-phenoxymethyl-7-oxo-4-thia-2,6-bicyclo[3,2,0]hept-2-en-6-yl]-α-(1-morpholino-2-bromoethylidene)acetate, adds 5% hydrochloric acid (36 ml), methanol (42.5 ml), and tetrahydrofuran (12.5 ml) to give clear solution. The solution is concentrated, the resulting solution being extracted with ethyl acetate, washed with saturated saline, dried over sodium sulfate, and concentrated to give residue (2.31 g). Purification of the residue by chromatography over silica gel containing 10% water gives benzyl 7β-phenoxyacetamido-3-hydroxy-3-cephem-4-carboxylate (1.11 g). m.p. 126°-127° C.

Sources & evidence

ORD record: ord-0fd80130490b457fb3ccba953c87b837
Source dataset: uspto-grants-1982_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04346218

Reaction notes

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