Boric Acid → 7-Amino-3-acetylthiomethyl-ceph-3-eme-4-carboxylic acid

HRID 1979620Notes

Reaction equation

HRID 1979620 reaction equation
[C:1]([OH:4])(=[S:3])[CH3:2].CC(O[CH2:9][C:10]1[CH2:19][S:18][C@@H:13]2[C@H:14]([NH2:17])[C:15](=[O:16])[N:12]2[C:11]=1[C:20]([OH:22])=[O:21])=O.B(O)(O)O>C(N(CC)CC)C.O>[NH2:17][CH:14]1[C:15](=[O:16])[N:12]2[C:11]([C:20]([OH:22])=[O:21])=[C:10]([CH2:9][S:3][C:1]([CH3:2])=[O:4])[CH2:19][S:18][C@H:13]12

Participants

6

Reactant 3

HCID 7628Boric AcidHCID 4413287-Aminocephalosporanic acidHCID 178418634HCID 178418634, compound2×

Product 1

HCID 886008887-Amino-3-acetylthiomethyl-ceph-3-eme-4-carboxylic acidYield 77%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8471TriethylamineSolvent2×

Conditions

Temperature
75 °C

Procedure

56.8 ml (0.8 mole) of thioacetic acid and 140 ml (1.0 mole) of triethylamine were added successively to three liters of water under stirring. The homogenous mixture was heated to 75° C. and there were added in one shot 100.0 g (0.368 mole) of 7-aminocephalosporanic acid (90%), causing a pH variation from 9.05 to 5.03. Thereafter there were added, first, 20 to 21 ml of triethylamine until a solution was formed and then 61.0 g of boric acid. Stirring was continued at 70° C. for 60 minutes and the reaction isoelectric pH was checked, regulating the variation from 5.80 to 5.60 by gradual addition of 10.9 ml of thioacetic acid over a period of about 30 minutes. During the last 15 minutes, the pH varied to a virtually constant value of 5.70. The precipitation increased during the reaction and was completed at 60° C. and the pH was adjusted to 4.80 (25° C.) by the addition of about 300 ml of 1N hydrochloric acid. The solid was filtered, washed successively with water and acetone to give 73.5 g of the compound of the title, with a 77% yield. It turned brown at about 215° C. and decomposed at 228° C. (polarised light). The excess thioacetic acid was recovered from the mother liquors at pH 1.0 by extraction with an organic solvent.

Workup

  1. additionThereafter there were added
  2. stirringStirring
  3. customDuring the last 15 minutes
  4. customThe precipitation
  5. temperatureincreased during the reaction
  6. customwas completed at 60° C.
  7. additionthe pH was adjusted to 4.80 (25° C.) by the addition of about 300 ml of 1N hydrochloric acid
  8. filtrationThe solid was filtered
  9. washwashed successively with water and acetone

Sources & evidence

ORD record
ord-812465f7eafb4d8fbb462665647b9f84
Source dataset
uspto-grants-1984_11
Patent number
US04481357

Reaction notes

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