4-Methylmorpholine → HCID 131711504, compound

HRID 1742148Notes

Reaction equation

HRID 1742148 reaction equation
ClC(OCC(C)C)=O.[C:9]([NH:28][C:29]1[S:30][CH:31]=[C:32]([C:34](=[N:38][O:39][CH2:40][CH:41]=[CH2:42])[C:35](O)=[O:36])[N:33]=1)([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CN1CCOCC1.[CH3:50][C:51]([O:53][CH2:54][C:55]1[CH2:64][S:63][C@@H:58]2[C@H:59]([NH2:62])[C:60](=[O:61])[N:57]2[C:56]=1[C:65]([OH:67])=[O:66])=[O:52]>C(N(CC)CC)C.C(Cl)Cl.O1CCCC1>[C:51]([O:53][CH2:54][C:55]1[CH2:64][S:63][C@@H:58]2[CH:59]([NH:62][C:35](=[O:36])[C:34]([C:32]3[N:33]=[C:29]([NH:28][C:9]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)([C:10]4[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=4)[C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)[S:30][CH:31]=3)=[N:38][O:39][CH2:40][CH:41]=[CH2:42])[C:60](=[O:61])[N:57]2[C:56]=1[C:65]([OH:67])=[O:66])(=[O:52])[CH3:50]

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 4413287-Aminocephalosporanic acidHCID 53877541HCID 53877541, compound

Product 1

HCID 131711504HCID 131711504, compound

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
-20 °C

Procedure

0.78 ml of isobutyl chloroformate were added at -20° C. to a mixture of 2.82 g of the product of Step B, 24 ml of dry tetrahydrofuran and 24 ml of methylene chloride to which 0.66 ml of N-methyl-morpholine had been added and the mixture was stirred at -20° C. for 3 minutes. The mixture was then cooled to -35° C. and a solution of 1.63 g of 7-amino-cephalosporanic acid 30 ml of methylene chloride and 1.68 ml of triethylamine was added thereto. The mixture was returned to room temperature during 3 hours and was evaporated to dryness. The residue was taken up in methylene chloride, and 50 ml of water and 15 ml of N hydrochloric acid were added. The mixture was stirred, decanted, and washed with water. The mixture was extracted with methylene chloride and the extracts were dried and vacuum filtered. The filter was rinsed with methylene chloride and the filtrate was evaporated to dryness. The residue was taken up in ethyl acetate and the solution was diluted with isopropyl ether, was stirred and was vacuum filtered. The recovered precipitate was rinsed with isopropyl ether to obtain 3.08 g of the anti isomer of 3-acetoxymethyl-7-[2-(2-tritylamino-4-thiazolyl)-2-(2-propenyloxyimino)-acetamido]-ceph-3-eme-4 -carboxylic acid. 3.59 g of the said product were dissolved in 15 ml of ethyl acetate and the solution was diluted with isopropyl ether, was stirred and was vacuum filtered to obtain 3.33 g of the said purified product.

Workup

  1. additionhad been added
  2. temperatureThe mixture was then cooled to -35° C.
  3. waitThe mixture was returned to room temperature during 3 hours
  4. customwas evaporated to dryness
  5. addition50 ml of water and 15 ml of N hydrochloric acid were added
  6. stirringThe mixture was stirred
  7. customdecanted
  8. washwashed with water
  9. extractionThe mixture was extracted with methylene chloride
  10. customthe extracts were dried
  11. filtrationvacuum filtered
  12. washThe filter was rinsed with methylene chloride
  13. customthe filtrate was evaporated to dryness
  14. additionthe solution was diluted with isopropyl ether
  15. stirringwas stirred
  16. filtrationfiltered
  17. washThe recovered precipitate was rinsed with isopropyl ether

Sources & evidence

ORD record
ord-0ba2c851716c48ae9376ff2162dbcb2f
Source dataset
uspto-grants-1994_08
Patent number
US05336776

Reaction notes

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