Hydrochloric Acid → 7-[2-(2-formamidothiazol-4-yl)-2-tert-butoxycarbonylmethoxyiminoacetamido]-3-[1-(2-tert-butoxycarbonylaminoethyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid

HRID 1154132Notes

Reaction equation

HRID 1154132 reaction equation
[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:13][O:14][CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:10]([OH:12])=O)[N:8]=1)=[O:2].P(Cl)(Cl)(Cl)=O.[NH2:28][CH:29]1[C:56](=[O:57])[N:31]2[C:32]([C:53]([OH:55])=[O:54])=[C:33]([CH2:36][S:37][C:38]3[N:42]([CH2:43][CH2:44][NH:45][C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[N:41]=[N:40][N:39]=3)[CH2:34][S:35][C@H:30]12.Cl>O1CCCC1.CC(C)=O.C(OCC)(=O)C.C(N(CC)CC)C.CN(C)C=O>[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:13][O:14][CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:10]([NH:28][CH:29]2[C:56](=[O:57])[N:31]3[C:32]([C:53]([OH:55])=[O:54])=[C:33]([CH2:36][S:37][C:38]4[N:42]([CH2:43][CH2:44][NH:45][C:46]([O:48][C:49]([CH3:51])([CH3:52])[CH3:50])=[O:47])[N:41]=[N:40][N:39]=4)[CH2:34][S:35][C@H:30]23)=[O:12])[N:8]=1)=[O:2]

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 24813Phosphorus oxychlorideHCID 543909512-t-Butoxycarbonylmethoxyimino-2-(2-formamidothiazol-4-yl)acetic acidHCID 704530537-amino-3-[1-(2-tert-butoxycarbonylaminoethyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid

Product 1

HCID 1317127827-[2-(2-formamidothiazol-4-yl)-2-tert-butoxycarbonylmethoxyiminoacetamido]-3-[1-(2-tert-butoxycarbonylaminoethyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acidYield 77.5%

Reagents, catalysts & solvents 5

HCID 180AcetoneSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-(2-Formamidothiazol-4-yl)-2-tert-butoxycarbonylmethoxyiminoacetic acid (syn isomer, 1.62 g.) was added to a solution of N,N-dimethylformamide (432 mg.) and phosphoryl chloride (905 mg.) in tetrahydrofuran (16 ml.) and treated in a similar manner to that of Example 6-(1). The solution was added to a solution of 7-amino-3-[1-(2-tert-butoxycarbonylaminoethyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid (3.0 g.) and triethylamine in 50% aqueous acetone (30 ml.) at -5° to -3° C. and pH 7 to 7.5 and stirred for 30 minutes. Ethyl acetate was added to the resultant solution and adjusted to pH 2.0 with 10% hydrochloric acid. After removing the insoluble substance by filtration, water and ethyl acetate were added to the filtrate. The ethyl acetate layer was separated and washed with saturated sodium chloride solution. The solution was dried over magnesium sulfate and concentrated in vacuo. The residue was pulverized with diethyl ether and the precipitates were collected by filtration to give 7-[2-(2-formamidothiazol-4-yl)-2-tert-butoxycarbonylmethoxyiminoacetamido]-3-[1-(2-tert-butoxycarbonylaminoethyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid (syn isomer, 2.93 g.).

Workup

  1. additiontreated in a similar manner to that of Example 6-(1)
  2. customAfter removing the insoluble substance
  3. filtrationby filtration, water and ethyl acetate
  4. additionwere added to the filtrate
  5. customThe ethyl acetate layer was separated
  6. washwashed with saturated sodium chloride solution
  7. dry with materialThe solution was dried over magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. filtrationthe precipitates were collected by filtration

Sources & evidence

ORD record
ord-53ed308cadc14b85a80e15cbfee42dc4
Source dataset
uspto-grants-1984_12
Patent number
US04487767

Reaction notes

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