Methanol → HCID 53642024, compound

HRID 376603Notes

Reaction equation

HRID 376603 reaction equation
P(Cl)(Cl)(Cl)(Cl)Cl.[CH3:7][C:8]1([CH3:44])[O:12][C@H:11]([C:13]2[CH2:14][S:15][C@@H:16]3[C@H:32]([NH:33]C(=O)CC4C=CC=CC=4)[C:31](=[O:43])[N:17]3[C:18]=2[C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)=[O:20])[CH2:10][CH2:9]1.CN1CCOCC1.CO>ClCCl.O>[NH2:33][C@@H:32]1[C:31](=[O:43])[N:17]2[C:18]([C:19]([O:21][CH2:22][C:23]3[CH:24]=[CH:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=3)=[O:20])=[C:13]([C@@H:11]3[CH2:10][CH2:9][C:8]([CH3:7])([CH3:44])[O:12]3)[CH2:14][S:15][C@H:16]12

Participants

7

Reactant 4

HCID 887MethanolHCID 79724-MethylmorpholineHCID 24819Phosphorus pentachlorideHCID 54312131HCID 54312131, compound

Product 1

HCID 53642024HCID 53642024, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-10 °C

Procedure

Phosphorus pentachloride (48mg, 0.23mmol) in dichloromethane (1.2ml) was added to 4-methoxybenzyl (6R,7R)-3-[(S)-5,5-dimethyltetrahydrofuran-2-yl]-7-phenylacetamidoceph-3-em-4-carboxylate (93mg, 0.15mmol) and N-methylmorpholine (34μl, 0.31mmol) in dichloromethane (3ml) at -25° C. The reaction was stirred at -10±5° C. for 45min., then methanol (0.5ml) was added, and stirring continued for 45min. at room temperature. Water (1ml) was then added, and the mixture vigorously stirred for a further 1h. After evaporation of the dichloromethane in vacuo, the pH of the aqueous residue was adjusted to 7 by the addition of ammonium hydroxide in the presence of ethyl acetate. The mixture was extracted with ethyl acetate (x2), dried and concentrated in vacuo. The residue was purified by chromatography on silica gel eluting with 70% ethyl acetate in hexane yielding the title compound (25mg, 39%); (Found: M+ 418.1566. C21H26N2O5S requires M+ 418.1562); vmax (CH2Cl2) 2970, 1777, 1721, 1613 and 1516cm-1 ; δH (CDCl3, 250MHz) 1.21 (3H, s), 1.27 (3H, s), 1.68-1.81 (3H, m), 2.25 (1H, m), 3.48 and 3.62 (2H, ABq, J 18.7Hz), 3.56 (2H, br s, exch.), 3.79 (3H, s), 4.73-5.25 (5H, m), 6.87 (2H, d, J 8.6Hz) and 7.30 (2H, d, J 8.6Hz).

Workup

  1. stirringstirring
  2. waitcontinued for 45min. at room temperature
  3. stirringthe mixture vigorously stirred for a further 1h
  4. customAfter evaporation of the dichloromethane in vacuo
  5. additionthe pH of the aqueous residue was adjusted to 7 by the addition of ammonium hydroxide in the presence of ethyl acetate
  6. extractionThe mixture was extracted with ethyl acetate (x2)
  7. customdried
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by chromatography on silica gel eluting with 70% ethyl acetate in hexane yielding the title compound (25mg, 39%)

Sources & evidence

ORD record
ord-1399c082e16c4c62b4c8231a9fac1a67
Source dataset
uspto-grants-2000_02
Patent number
US06020329

Reaction notes

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