Water → (6R,7R)-3-[(1-aminotetrazol-5-yl)sulfanylmethyl]-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

HRID 483025Notes

Reaction equation

HRID 483025 reaction equation
C(N(CC)CC)C.O.[NH2:9][C@@H:10]1[C:28](=[O:29])[N:12]2[C:13]([C:25]([OH:27])=[O:26])=[C:14]([CH2:17][S:18][C:19]3[N:23]([NH2:24])[N:22]=[N:21][N:20]=3)[CH2:15][S:16][C@H:11]12.[C:30]([NH:49][C:50]1[S:51][CH:52]=[C:53](/[C:55](=[N:68]/[O:69][CH3:70])/[C:56](ON2C3C=CC=CC=3N=N2)=[O:57])[N:54]=1)([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>CC(N(C)C)=O>[C:30]([NH:49][C:50]1[S:51][CH:52]=[C:53](/[C:55](=[N:68]/[O:69][CH3:70])/[C:56]([NH:9][C@@H:10]2[C:28](=[O:29])[N:12]3[C:13]([C:25]([OH:27])=[O:26])=[C:14]([CH2:17][S:18][C:19]4[N:23]([NH2:24])[N:22]=[N:21][N:20]=4)[CH2:15][S:16][C@H:11]23)=[O:57])[N:54]=1)([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)([C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 133675107beta-amino-3-(1-amino-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acidHCID 88675991benzotriazol-1-yl (2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetate

Product 1

HCID 178502831(6R,7R)-3-[(1-aminotetrazol-5-yl)sulfanylmethyl]-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidYield 57.7%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Procedure

To a solution of triethylamine (7.02 g, 69.4 mmol) and water (2.2 ml) in dimethylacetamide (72 ml) was added 7β-amino-3-[(1-amino-1H-tetrazol-5-yl)thiomethyl]-3-cephem-4-carboxylic acid (11.5 g, 34.7 mmol) at room temperature and the mixture was stirred to dissolve it. The mixture was cooled to -6° to -3° C. and a solution of 1-benzotriazolyl 2-(2-tritylaminothiazol-4-yl)-(Z)-2-methoxyiminoacetate (29.2 g, 52.1 mmol) in dimethylacetamide (120 ml) was added dropwise to the mixture and allowed to react at 5° C. for 17 hours. The reaction mixture was poured into ice-water (500 ml). The aqueous layer was washed with ethyl acetate (100 ml)--tetrahydrofuran (50 ml) and adjusted to pH 3 with 20% aqueous sulfuric acid. Precipitated material was extracted with ethyl acetate (200 ml)--tetrahydrofuran (100 ml). The organic layer was filtered to remove insoluble material, washed with water, dried over magnesium sulfate and evaporated under reduced pressure. The residue was treated with ether to give pale yellow substance of 7β-[2-(2-tritylaminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3-[(1-amino-1H-tetrazol-5-yl)thiomethyl]-3-cephem-4-carboxylic acid (15.1 g, 57.7%), mp~175° C. (decomposition).

Workup

  1. dissolutionto dissolve it
  2. temperatureThe mixture was cooled to -6° to -3° C.
  3. customto react at 5° C. for 17 hours
  4. washThe aqueous layer was washed with ethyl acetate (100 ml)
  5. extractionPrecipitated material was extracted with ethyl acetate (200 ml)
  6. filtrationThe organic layer was filtered
  7. customto remove insoluble material
  8. washwashed with water
  9. dry with materialdried over magnesium sulfate
  10. customevaporated under reduced pressure
  11. additionThe residue was treated with ether

Sources & evidence

ORD record
ord-b4817334020946b59c28e1033e6fb88e
Source dataset
uspto-grants-1986_03
Patent number
US04576938

Reaction notes

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