Methanol → HCID 56985057, compound

HRID 376602Notes

Reaction equation

HRID 376602 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 (754mg, 3.62mmol) in dichloromethane (19ml) was added to 4-methoxybenzyl (6R,7R)-3-(5-methyltetrahydrofuran-2-yl)-7-phenylacetamidoceph-3-em-4-carboxylate (containing some of the Δ2-isomer) (1.26g, 2.41mmol) and N-methylmorpholine (531gl, 4.83mmol) in dichloromethane (15ml) at -25° C. The reaction was stirred at -10±5° C. for 45 min., then methanol (5ml) was added, and stirring was continued for 45 min. at room temperature. Water (10ml) 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 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 (310mg, 32%) as a pale yellow foam; (Found: M+, 404.1394. C20H24N2O5S requires M+ 404.1406); vmax (CH2Cl2) 3412, 1776, 1721, 1613, 1516 and 1393cm -1 ; δH (CDCl3, 250MHz), 1.24 (3H, d, J 5.8Hz), 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 17.7Hz), 3.78 (3H, s), 3.98 (1H, m), 4.88 (1H, d, J 5.0Hz), 4.93-5.04 (2H, m), 5.17 (2H, s), 6.87 (2H, d, J 8.6Hz), 7.32 (2H, d, J 8.6Hz).

Workup

  1. stirringstirring
  2. waitwas continued for 45 min. 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 30, 50, 70, 80 and 100% ethyl acetate in hexane

Sources & evidence

ORD record
ord-5594e50331494a40ba51f613b54b4f28
Source dataset
uspto-grants-2000_02
Patent number
US06020329

Reaction notes

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