Methanol → HCID 53642024, compound

HRID 612306Notes

Reaction equation

HRID 612306 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 (48 mg, 0.23 mmol) in dichloromethane (1.2 ml) was added to 4-methoxybenzyl (6R,7R)-3-[(S)-5,5-dimethyltetrahydrofuran-2-yl]-7-phenylacetamidoceph-3-em-4-carboxylate (93 mg, 0.15 mmol) and N-methylmorpholine (34 μl, 0.31 mmol) in dichloromethane (3 ml) at -25° C. The reaction was stirred at -10±5° C. for 45 min., then methanol (0.5 ml) was added, and stirring continued for 45 min. at room temperature. Water (1 ml) was then added, and the mixture vigorously stirred for a further 1 h. 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 (25 mg, 39%); (Found: M+ 418.1566. C21H26N2O5S requires M+ 418.1562); νmax (CH2Cl2) 2970, 1777, 1721, 1613 and 1516 cm-1 ; δH (CDCl3, 250 MHz) 1.21 (3 H, s), 1.27 (3 H, s), 1.68-1.81 (3 H, m), 2.25 (1 H, m), 3.48 and 3.62 (2 H, ABq, J 18.7 Hz), 3.56 (2 H, br s, exch.), 3.79 (3 H, s), 4.73-5.25 (5 H, m), 6.87 (2 H, d, J 8.6 Hz) and 7.30 (2 H, d, J 8.6 Hz).

Workup

  1. stirringstirring
  2. waitcontinued for 45 min. at room temperature
  3. stirringthe mixture vigorously stirred for a further 1 h
  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 (25 mg, 39%)

Sources & evidence

ORD record
ord-0e86c3bda9384504890b8a56edb82b04
Source dataset
uspto-grants-1999_12
Patent number
US06001997

Reaction notes

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