2-Thiopheneacetyl chloride → Cephalothin

HRID 1390668Notes

Reaction equation

HRID 1390668 reaction equation
[CH3:1][C:2]([O:4][CH2:5][C:6]1[CH2:15][S:14][C@@H:9]2[C@H:10]([NH2:13])[C:11](=[O:12])[N:8]2[C:7]=1[C:16]([OH:18])=[O:17])=[O:3].ClB1OCCO1.[S:25]1[CH:29]=[CH:28][CH:27]=[C:26]1[CH2:30][C:31](Cl)=[O:32].C(=O)(O)[O-].[Na+]>C(Cl)Cl.O.C(N(CC)CC)C>[CH3:1][C:2]([O:4][CH2:5][C:6]1[CH2:15][S:14][C@@H:9]2[C@H:10]([NH:13][C:31]([CH2:30][C:26]3[S:25][CH:29]=[CH:28][CH:27]=3)=[O:32])[C:11](=[O:12])[N:8]2[C:7]=1[C:16]([OH:18])=[O:17])=[O:3]

Participants

8

Reactant 4

HCID 1623622-Thiopheneacetyl chlorideHCID 4413287-Aminocephalosporanic acidHCID 516892Sodium BicarbonateHCID 53262932-chloro-1,3,2-dioxaborolane

Product 1

HCID 6024CephalothinYield 70.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
-40 °C

Procedure

2.72 g 7-ACA were suspended in 60 ml methylene chloride, then adding 2.2 g triethylamine. After cooling to -40° C., 21 ml of a 1,1 molar solution of ethylene chloroboronate in methylene chloride was poured into the mixture. The mixture was heated to -10° C. and 1.9 g of 2-thienylacetic acid chloride were poured into the mixture. Stirring was maintained for 2 hours at 0° C. 40 ml water were poured therein and after unmixing, the organic phase was added with a solution of sodium bicarbonate to constant pH 7.5. The phases were separated and the aqueous phase was washed with 50 ml methylene chloride. The aqueous phase was treated with decolouring carbon and dicalite. The product was filtered and after addition of 65 ml acetone the filtrate was acidified to pH 2. The product was allowed to crystallize at +5° C. for 2 hours, then filtered, washing with water and acetone. After vacuum drying at 40° C. 2.8 g 7-(2-thienylacetamido) cephalosporanic acid were obtained.

Workup

  1. temperatureThe mixture was heated to -10° C.
  2. temperaturewas maintained for 2 hours at 0° C
  3. customThe phases were separated
  4. washthe aqueous phase was washed with 50 ml methylene chloride
  5. additionThe aqueous phase was treated with decolouring carbon and dicalite
  6. filtrationThe product was filtered
  7. additionafter addition of 65 ml acetone the filtrate
  8. customto crystallize at +5° C. for 2 hours
  9. filtrationfiltered
  10. washwashing with water and acetone
  11. customAfter vacuum drying at 40° C

Sources & evidence

ORD record
ord-88f754c510084111a5f8d14a365a51b7
Source dataset
uspto-grants-1979_02
Patent number
US04139702

Reaction notes

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