Methanol → HCID 53642024, compound

HRID 1421823Notes

Reaction equation

HRID 1421823 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
5 °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 (×2), 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 (3H, s), 1.27 (3H, s), 1.68-1.81 (3H, m), 2.25 (1H, m), 3.48 and 3.62 (2H, ABq, J 18.7 Hz), 3.56 (2H, br s, exch.), 3.79 (3H, s), 4.73-5.25 (5H, m), 6.87 (2H, d, J 8.6 Hz) and 7.30 (2H, 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 (×2)
  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-edfa2b14d3fd4237bc3ecdb663b2295e
Source dataset
uspto-grants-2000_06
Patent number
US06077952

Reaction notes

Loading…