Triethylamine → HCID 70604733, compound

HRID 2164134Notes

Reaction equation

HRID 2164134 reaction equation
[CH3:1][S:2][CH:3]([C:7]1[O:8][CH:9]=[CH:10][CH:11]=1)[C:4]([OH:6])=O.C(N(CC)CC)C.C(Cl)(=O)C(C)(C)C.[CH3:26][C:27]([O:29][CH2:30][C:31]1[CH2:40][S:39][C@@H:34]2[C@H:35]([NH2:38])[C:36](=[O:37])[N:33]2[C:32]=1[C:41]([OH:43])=[O:42])=[O:28]>O1CCCC1.ClCCl>[CH3:1][S:2][CH:3]([C:7]1[O:8][CH:9]=[CH:10][CH:11]=1)[C:4]([NH:38][CH:35]1[C:36](=[O:37])[N:33]2[C:32]([C:41]([OH:43])=[O:42])=[C:31]([CH2:30][O:29][C:27](=[O:28])[CH3:26])[CH2:40][S:39][C@H:34]12)=[O:6]

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 62493Pivaloyl chlorideHCID 4413287-Aminocephalosporanic acidHCID 13208968HCID 13208968, compound

Product 1

HCID 70604733HCID 70604733, compoundYield 56.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-11 °C

Procedure

α-Methylthio(2-furyl)acetic acid (2.00 g) was suspended in 120 ml of tetrahydrofuran, and 1.62 ml of triethylamine was added. The mixture was cooled to -10 to -12° C. To the mixture was added a solution of 1.40 g of pivaloyl chloride in 20 ml of tetrahydrofuran over the course of 10 minutes, and the mixture was stirred for 30 minutes. A solution obtained by stirring 3.80 g of 7-ACA and 1.96 ml of triethylamine in 180 ml of dichloromethane was added dropwise over the course of 35 minutes at below -10° C. The mixture was stirred for 1 hour at this temperature, for 1 hour at 0 to 3° C., and then for 1 hour at room temperature. The insoluble matter was then separated by filtration. The filtrate was acidified with 1N hydrochloric acid, and extracted with dichloromethane. The dichloromethane layer was extracted once with 80 ml, 40 ml and 20 ml of a 3% aqueous solution of sodium bicarbonate. The water layer was acidified with 1N hydrochloric acid, and extracted with 200 ml of ethyl acetate and then with 100 ml of ethyl acetate. The ethyl acetate layer was washed four times with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Petroleum ether was added to the oily residue, and it was powderized. By filtration, 2.8 g of a powder was obtained. The powder was chromatographed on a 1-liter column of an adsorbent resin HP-20 (a product of Mitsubishi Chemical Co. Ltd.) using acetone/water as an eluant to afford 0.85 g of the final product having one spot on a silica gel thin-layer chromatogram.

Workup

  1. customA solution obtained
  2. additionwas added dropwise over the course of 35 minutes at below -10° C
  3. stirringThe mixture was stirred for 1 hour at this temperature, for 1 hour at 0 to 3° C.
  4. waitfor 1 hour at room temperature
  5. customThe insoluble matter was then separated by filtration
  6. extractionextracted with dichloromethane
  7. extractionThe dichloromethane layer was extracted once with 80 ml, 40 ml and 20 ml of a 3% aqueous solution of sodium bicarbonate
  8. extractionextracted with 200 ml of ethyl acetate
  9. washThe ethyl acetate layer was washed four times with a saturated aqueous solution of sodium chloride
  10. dry with materialdried over anhydrous sodium sulfate
  11. concentrationconcentrated under reduced pressure
  12. additionPetroleum ether was added to the oily residue, and it
  13. filtrationBy filtration

Sources & evidence

ORD record
ord-08f59829ea2041368d03f38b750e41f3
Source dataset
uspto-grants-1979_01
Patent number
US04137406

Reaction notes

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