4-Methylmorpholine → HCID 131718638, compound

HRID 1742143Notes

Reaction equation

HRID 1742143 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][CH3:41])[C:35]([OH:37])=O)[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.[CH3:49][C:50]([O:52][CH2:53][C:54]1[CH2:63][S:62][C@@H:57]2[C@H:58]([NH2:61])[C:59](=[O:60])[N:56]2[C:55]=1[C:64]([OH:66])=[O:65])=[O:51]>C(Cl)Cl.C(N(CC)CC)C.O1CCCC1>[C:50]([O:52][CH2:53][C:54]1[CH2:63][S:62][C@@H:57]2[CH:58]([NH:61][C:35](=[O:37])[C:34]([C:32]3[N:33]=[C:29]([NH:28][C:9]([C:10]4[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=4)([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)[S:30][CH:31]=3)=[N:38][O:39][CH2:40][CH3:41])[C:59](=[O:60])[N:56]2[C:55]=1[C:64]([OH:66])=[O:65])(=[O:51])[CH3:49]

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 4413287-Aminocephalosporanic acidHCID 54056605HCID 54056605, compound

Product 1

HCID 131718638HCID 131718638, compound

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
-20 °C

Procedure

1.17 ml of isobutyl chloroformate was added dropwise under an inert atmosphere to a mixture of 4.1 g of the product of Step C, 36 ml of tetrahydrofuran, 27 ml of methylene chloride and 0.99 ml of N-methyl-morpholine cooled to -20° C. and after standing at -20° C. for 3 minutes, the mixture was cooled to -35° C. and a solution of 2.45 g of 7-aminocephalosporanic acid in 45 ml of methylene chloride and 252 ml of triethylamine were added thereto. The mixture stood for 21/2 hours with spontaneous heating and was then evaporated to dryness. The residue was taken up in a mixture of methylene chloride, water and N hydrochloric acid with a pH of 1-2 and the mixture was extracted with methylene chloride. The organic extracts were washed with water, dried and vacuum filtered. The filtrate was evaporated to dryness and the residue was taken up in ethyl acetate. The solution was diluted with isopropyl ether and was stirred and vacuum filtered The recovered product was rinsed with isopropyl ether and dri to obtain 4.87 g of the anti isomer of 3-acetoxymethyl-7-[2-(2-tritylamino-4-thiazolyl)-2-ethoxyiminoacetamido]-ceph-3-em-4-carboxylic acid. The said product was dissolved in 10 ml of hot ethyl acetate and the solution was slowly diluted with isopropyl ether. The mixture was stirred and was vacuum filtered and the recevered product was rinsed with isopropyl ether and dried to obtain 4.53 g of purified product.

Workup

  1. temperaturethe mixture was cooled to -35° C.
  2. custom2 hours
  3. temperaturewith spontaneous heating
  4. customwas then evaporated to dryness
  5. additionThe residue was taken up in a mixture of methylene chloride, water and N hydrochloric acid with a pH of 1-2
  6. extractionthe mixture was extracted with methylene chloride
  7. washThe organic extracts were washed with water
  8. customdried
  9. filtrationvacuum filtered
  10. customThe filtrate was evaporated to dryness
  11. additionThe solution was diluted with isopropyl ether
  12. filtrationvacuum filtered The recovered product
  13. washwas rinsed with isopropyl ether and dri

Sources & evidence

ORD record
ord-f382833fa700481ebfa33759a8b230c1
Source dataset
uspto-grants-1994_08
Patent number
US05336776

Reaction notes

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