Formic Acid → 7-[2-carboxymethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-[1-(2-propynyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid

HRID 1995799Notes

Reaction equation

HRID 1995799 reaction equation
C([O:5][C:6]([CH2:8][O:9][N:10]=[C:11]([C:37]1[N:41]=[C:40]([NH2:42])[S:39][N:38]=1)[C:12]([NH:14][CH:15]1[C:35](=[O:36])[N:17]2[C:18]([C:32]([OH:34])=[O:33])=[C:19]([CH2:22][S:23][C:24]3[N:28]([CH2:29][C:30]#[CH:31])[N:27]=[N:26][N:25]=3)[CH2:20][S:21][C@H:16]12)=[O:13])=[O:7])(C)(C)C.C(O)=O.Cl>C(=O)(O)[O-].[Na+]>[C:6]([CH2:8][O:9][N:10]=[C:11]([C:37]1[N:41]=[C:40]([NH2:42])[S:39][N:38]=1)[C:12]([NH:14][CH:15]1[C:35](=[O:36])[N:17]2[C:18]([C:32]([OH:34])=[O:33])=[C:19]([CH2:22][S:23][C:24]3[N:28]([CH2:29][C:30]#[CH:31])[N:27]=[N:26][N:25]=3)[CH2:20][S:21][C@H:16]12)=[O:13])([OH:7])=[O:5]

Participants

5

Reactant 3

HCID 284Formic AcidHCID 313Hydrochloric Acid2×HCID 1317130887-[2-tert-butoxycarbonylmethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-[1-(2-propynyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid

Product 1

HCID 1317130997-[2-carboxymethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-[1-(2-propynyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acidYield 31.3%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of 7-[2-tert-butoxycarbonylmethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-[1-(2-propynyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid (syn isomer)(3.5 g), formic acid (35 ml) and conc. hydrochloric acid (1.0 ml) was stirred for an hour at room temperature. The reaction mixture was evaporated and the residue was pulverized with diethyl ether and dried. Thus obtained product (3.2 g) was dissolved in an aqueous solution of sodium bicarbonate and ethyl acetate was added thereto. The mixture was adjusted to pH 1 with 6 N hydrochloric acid and then filtered. The ethyl acetate layer was separated from the filtrate, washed with a saturated aqueous solution of sodium chloride, treated with activated charcoal, dried over magnesium sulfate and then evaporated. The residue was pulverized with diethyl ether and dried to give a crude product (2.0 g). The product was dissolved in an aqueous solution of sodium bicarbonate and the solution was acidified with 6 N hydrochloric acid. The precipitates were collected by filtration, washed with water and then dried to give 7-[2-carboxymethoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-[1-(2-propynyl)-1H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (1.0 g), mp. 160° to 165° C. (dec.).

Workup

  1. customThe reaction mixture was evaporated
  2. customdried
  3. dissolutionThus obtained product (3.2 g) was dissolved in an aqueous solution of sodium bicarbonate and ethyl acetate
  4. additionwas added
  5. filtrationfiltered
  6. customThe ethyl acetate layer was separated from the filtrate
  7. washwashed with a saturated aqueous solution of sodium chloride
  8. additiontreated with activated charcoal
  9. dry with materialdried over magnesium sulfate
  10. customevaporated
  11. customdried
  12. customto give a crude product (2.0 g)
  13. filtrationThe precipitates were collected by filtration
  14. washwashed with water
  15. customdried

Sources & evidence

ORD record
ord-1dd110bd644d4881a94340eaac69e3b4
Source dataset
uspto-grants-1983_09
Patent number
US04405617

Reaction notes

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