Methanol → HCID 56985057, compound

HRID 1421822Notes

Reaction equation

HRID 1421822 reaction equation
P(Cl)(Cl)(Cl)(Cl)Cl.[CH3:7][CH:8]1[O:12][CH: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@H:8]([CH3:7])[O:12]3)[CH2:14][S:15][C@H:16]12

Participants

7

Reactant 4

HCID 887MethanolHCID 79724-MethylmorpholineHCID 24819Phosphorus pentachlorideHCID 131721508HCID 131721508, compound

Product 1

HCID 56985057HCID 56985057, compoundYield 32%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-10 °C

Procedure

Phosphorus pentachloride (754 mg, 3.62 mmol) in dichloromethane (19 ml) was added to 4-methoxybenzyl (6R,7R)-3-(5-methyltetrahydrofuran-2-yl)-7-phenylacetamidoceph-3-em-4-carboxylate (containing some of the Δ2-isomer) (1.26 g, 2.41 mmol) and N-methylmorpholine (531 μl, 4.83 mmol) in dichloromethane (15 ml) at -25° C. The reaction was stirred at -10±5° C. for 45 min., then methanol (5 ml) was added, and stirring was continued for 45 min. at room temperature. Water (10 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 30, 50, 70, 80 and 100% ethyl acetate in hexane yielding 4-methoxybenzyl (6R,7R)-7-amino-3-[(5S,2S)-5-methyltetrahydrofuran-2-yl]ceph-3-em-4-carboxylate (310 mg, 32%) as a pale yellow foam; (Found: M+, 404.1394. C20H24N2O5S requires M+ 404.1406); νmax (CH2Cl2) 3412, 1776, 1721, 1613, 1516 and 1393 cm-1 ; δH (CDCl3, 250 MHz), 1.24 (3H, d, J 5.8 Hz), 1.48 (1H, m), 1.69 (1H, m), 2.02 (3H, m, 2H exch.), 2.25 (1H, m), 3.45 and 3.60 (2H, ABq, J 17.7 Hz), 3.78 (3H, s), 3.98 (1H, m), 4.88 (1H, d, J 5.0 Hz), 4.93-5.04 (2H, m), 5.17 (2H, s), 6.87 (2H, d, J 8.6 Hz), 7.32 (2H, d, J 8.6 Hz).

Workup

  1. stirringstirring
  2. waitwas continued 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 30, 50, 70, 80 and 100% ethyl acetate in hexane

Sources & evidence

ORD record
ord-af3c58d13d3f4c7ab0529e8e28942887
Source dataset
uspto-grants-2000_06
Patent number
US06077952

Reaction notes

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