Ethyl Acetate → n-Hexanoyloxymethyl 7-(2-[2-amino-4-thiazolyl)-2-methoxyiminoacetamido]-3-chloro-3-cephem-4-carboxylate

HRID 621267Notes

Reaction equation

HRID 621267 reaction equation
Cl.[NH2:2][C:3]1[S:4][CH:5]=[C:6]([C:8](=[N:25][O:26][CH3:27])[C:9]([NH:11][CH:12]2[C:23](=[O:24])[N:14]3[C:15]([C:20]([OH:22])=[O:21])=[C:16]([Cl:19])[CH2:17][S:18][C@H:13]23)=[O:10])[N:7]=1.[Na].[C:29]([O:36][CH2:37]I)(=[O:35])[CH2:30][CH2:31][CH2:32][CH2:33][CH3:34].C(OCC)(=O)C>O.CN(C)C=O>[NH2:2][C:3]1[S:4][CH:5]=[C:6]([C:8](=[N:25][O:26][CH3:27])[C:9]([NH:11][CH:12]2[C:23](=[O:24])[N:14]3[C:15]([C:20]([O:22][CH2:37][O:36][C:29](=[O:35])[CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])=[O:21])=[C:16]([Cl:19])[CH2:17][S:18][C@H:13]23)=[O:10])[N:7]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 5360545SodiumHCID 12775069Iodomethyl hexanoateHCID 1317124337-[2-(2-Amino-4-thiazolyl)-2-methoxyiminoacetamido]-3-chloro-3-cephem-4-carboxylic acid hydrochloride

Product 1

HCID 131712435n-Hexanoyloxymethyl 7-(2-[2-amino-4-thiazolyl)-2-methoxyiminoacetamido]-3-chloro-3-cephem-4-carboxylateYield 55.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent2×

Procedure

7-[2-(2-Amino-4-thiazolyl)-2-methoxyiminoacetamido]-3-chloro-3-cephem-4-carboxylic acid hydrochloride (syn-isomer: 1.5 g.) and sodium bicarbonte (0.56 g.) were dissolved in water (50 ml.) at room temperature with stirring and lyophilized. A solution of iodomethyl hexanoate (0.93 g.) in dimethylformamide (5 ml.) was added dropwise to a solution of the product obtained above in dimethylformamide (15 ml.) at -5° C. and stirred at the same temperature for 30 minutes. Ethyl acetate (50 ml.) and water (100 ml.) were added to the resultant solution and the ethyl acetate layer was separated. The aqueous layer was extracted with ethyl acetate (50 ml.) twice. The extracts were combined with the ethyl acetate layer, washed with a saturated aqueous solution of sodium bicarbonate three times and a saturated aqueous solution of sodium chloride three times in turn, dried over magnesium sulfate, treated with activated charcoal and then concentrated under reduced pressure. After washing the concentrate with n-hexane (50 ml.), n-hexane (50 ml.) and diethylether (25 ml.) were added to the residue and allowed to stand in a refrigerator overnight. The precipitating powder was collected by filtration, washed with n-hexane and dried to give a mixture (1.0 g.) of n-hexanoyloxymethyl 7-[2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido]-3-chloro-3-cephem-4-carboxylate (syn-isomer) and n-hexanoyloxymethyl 7-[2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido]-3-chloro-2-cephem-4-carboxylate (syn-isomer.)

Workup

  1. stirringstirred at the same temperature for 30 minutes
  2. customthe ethyl acetate layer was separated
  3. extractionThe aqueous layer was extracted with ethyl acetate (50 ml.) twice
  4. washwashed with a saturated aqueous solution of sodium bicarbonate three times
  5. dry with materiala saturated aqueous solution of sodium chloride three times in turn, dried over magnesium sulfate
  6. additiontreated with activated charcoal
  7. concentrationconcentrated under reduced pressure
  8. washAfter washing the
  9. concentrationconcentrate with n-hexane (50 ml.), n-hexane (50 ml.) and diethylether (25 ml.)
  10. additionwere added to the residue
  11. customto stand in a refrigerator overnight
  12. filtrationThe precipitating powder was collected by filtration
  13. washwashed with n-hexane
  14. customdried

Sources & evidence

ORD record
ord-30debddda9734fb1b9befda3cee237bd
Source dataset
uspto-grants-1989_04
Patent number
US04822888

Reaction notes

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