Methanol → Diphenylmethyl 7beta-Amino-3-(6-methyl-2-oxo-2H-pyran-4-ylthiomethyl)ceph-3-em-4-carboxylate

HRID 467378Notes

Reaction equation

HRID 467378 reaction equation
[CH3:1][C:2]1[O:7][C:6](=[O:8])[CH:5]=[C:4]([S:9][CH2:10][C:11]2[CH2:12][S:13][C@@H:14]3[C@H:34]([NH:35]C(=O)CC4C=CC=CC=4)[C:33](=[O:45])[N:15]3[C:16]=2[C:17]([O:19][CH:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[CH:3]=1.CN1CCOCC1.P(Cl)(Cl)(Cl)(Cl)Cl.CO>ClCCl.O>[NH2:35][C@@H:34]1[C:33](=[O:45])[N:15]2[C:16]([C:17]([O:19][CH:20]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)=[O:18])=[C:11]([CH2:10][S:9][C:4]3[CH:3]=[C:2]([CH3:1])[O:7][C:6](=[O:8])[CH:5]=3)[CH2:12][S:13][C@H:14]12

Participants

7

Reactant 4

HCID 887MethanolHCID 79724-MethylmorpholineHCID 24819Phosphorus pentachlorideHCID 67908899diphenylmethyl 3-(6-methyl-2-oxo-2H-pyran-4-ylthiomethyl)-7beta-phenylacetamidoceph-3-em-4-carboxylate

Product 1

HCID 67908188Diphenylmethyl 7beta-Amino-3-(6-methyl-2-oxo-2H-pyran-4-ylthiomethyl)ceph-3-em-4-carboxylateYield 95%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

A stirred solution of diphenylmethyl 3-(6-methyl-2-oxo-2H-pyran-4-ylthiomethyl)-7β-phenylacetamidoceph-3-em-4-carboxylate (1.55 g) in dichloromethane (20 ml) was cooled to -15° to -20° C. and N-methylmorpholine (0.54 ml) was added followed by a solution of phosphorus pentachloride in dichloromethane (19 ml of a solution containing 40 mg ml-1). The mixture was maintained at the same temperature for 0.5 h and then methanol (4.9 ml) was added and the mixture stirred at room temperature for 0.5 h. Water (6.6 ml) was then added and the mixture was vigorously stirred for 0.5 h. Most of the dichloromethane was removed on a rotary evaporator and the residue was stirred with water and ethyl acetate. The pH of the aqueous phase was adjusted to 6.2 with 1N aqueous ammonia. The organic phase was separated, washed with water and brine, dried over magnesium sulphate and evaporated. The product (1.20 g) was isolated by column chromatography using gradient elution (Kieselgel 1:1 hexane:ethyl acetate going to neat ethyl acetate). υmax (CHCl3) 1785, 1710cm-1 δ(CDCl3) 1.79 (2H, S). 2.18 (3H, S) 3.42 (1H, d, J 18.2Hz), 3.61 (1H, d, J 18.3Hz), 3.80 (1H, d, J 12.2Hz), 3.90 (1H, d, J 12.2Hz), 4.80 (1H, d, J 5.2Hz), 4.96 (1H, d, J 5.1Hz), 5.66 (1H, d, J ca 1Hz), 5.78 (1H, d, J ca 1Hz), 7.00 (1H, s), 7.2-7.45 (10H, m). [Mass spectrum: +ve ion (3NOBA, Na+) MNa+ 543].

Workup

  1. temperatureThe mixture was maintained at the same temperature for 0.5 h
  2. stirringthe mixture was vigorously stirred for 0.5 h
  3. customMost of the dichloromethane was removed on a rotary evaporator
  4. stirringthe residue was stirred with water and ethyl acetate
  5. customThe organic phase was separated
  6. washwashed with water and brine
  7. dry with materialdried over magnesium sulphate
  8. customevaporated

Sources & evidence

ORD record
ord-09a8e21c8dc94580b87ba1f83c384c33
Source dataset
uspto-grants-1992_10
Patent number
US05158946

Reaction notes

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