Diisopropyl Ether → Benzhydryl 7-[2-tert-butoxycarbonylmethoxyimino-2-(2-formamidothiazol-4-yl)-acetamido]-3-vinyl-3-cephem-4-carboxylate

HRID 1154216Notes

Reaction equation

HRID 1154216 reaction equation
[C:1]([O:5][C:6]([CH2:8][O:9][N:10]=[C:11]([C:15]1[N:16]=[C:17]([NH:20][CH:21]=[O:22])[S:18][CH:19]=1)[C:12]([OH:14])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].P(Cl)(Cl)(Cl)=O.Cl.[NH2:29][CH:30]1[C:55](=[O:56])[N:32]2[C:33]([C:39]([O:41][CH:42]([C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)=[O:40])=[C:34]([CH:37]=[CH2:38])[CH2:35][S:36][C@H:31]12.C[Si](CC(N)=O)(C)C.C(OC(C)C)(C)C>O1CCCC1.C(OCC)(=O)C.O.CN(C)C=O>[C:1]([O:5][C:6]([CH2:8][O:9][N:10]=[C:11]([C:15]1[N:16]=[C:17]([NH:20][CH:21]=[O:22])[S:18][CH:19]=1)[C:12]([NH:29][CH:30]1[C:55](=[O:56])[N:32]2[C:33]([C:39]([O:41][CH:42]([C:43]3[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=3)[C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)=[O:40])=[C:34]([CH:37]=[CH2:38])[CH2:35][S:36][C@H:31]12)=[O:14])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

10

Reactant 5

HCID 7914Diisopropyl EtherHCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 12818005Benzhydryl 7-amino-3vinyl-3cephem-4-carboxylate hydrochlorideHCID 543909512-t-Butoxycarbonylmethoxyimino-2-(2-formamidothiazol-4-yl)acetic acid

Product 1

HCID 131713176Benzhydryl 7-[2-tert-butoxycarbonylmethoxyimino-2-(2-formamidothiazol-4-yl)-acetamido]-3-vinyl-3-cephem-4-carboxylateYield 93.9%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

The activated acid, which was prepared from 2-tert-butoxycarbonylmethoxyimino-2-(2-formamidothiazol-4-yl)acetic acid (syn isomer) (13.8 g), N,N-dimethylformamide (3.66 g) and phosphorus oxychloride (7.7 g) in tetrahydrofuran (80 ml) in a conventional manner, was added to a solution of benzhydryl 7-amino-3-vinyl-3-cephem-4-carboxylate hydrochloride (15 g) and trimethylsilylacetamide (32 g) in ethyl acetate (150 ml) at -20° C. with stirring, and the stirring was continued at the same temperature for half an hour. After addition of water (100 ml), the ethyl acetate layer was separated out, and washed with an aqueous solution of sodium chloride, an aqueous solution of sodium bicarbonate and then an aqueous solution of sodium chloride in turn, followed by drying over anhydrous magnesium sulfate. Removal of the solvent gave an oil, which was pulverized with diisopropyl ether and washed with the same to obtain benzhydryl 7-[2-tert-butoxycarbonylmethoxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-vinyl-3-cephem-4-carboxylate (syn isomer) (23.1 g), mp 101° C. (dec.).

Workup

  1. waitthe stirring was continued at the same temperature for half an hour
  2. customthe ethyl acetate layer was separated out
  3. washwashed with an aqueous solution of sodium chloride
  4. dry with materialby drying over anhydrous magnesium sulfate
  5. customRemoval of the solvent
  6. customgave an oil, which
  7. washwashed with the same

Sources & evidence

ORD record
ord-af711ee8d03047b5b79d8f1679efeb80
Source dataset
uspto-grants-1984_12
Patent number
US04487927

Reaction notes

Loading…