Methanol → HCID 67908473, compound

HRID 467377Notes

Reaction equation

HRID 467377 reaction equation
[Cl:1][C:2]1[C:3](=[O:44])[O:4][CH2:5][C:6]=1[S:7][CH2:8][C:9]1[CH2:10][S:11][C@@H:12]2[C@H:32]([NH:33]C(=O)CC3C=CC=CC=3)[C:31](=[O:43])[N:13]2[C:14]=1[C:15]([O:17][CH:18]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16].CN1CCOCC1.P(Cl)(Cl)(Cl)(Cl)Cl.CO>ClCCl.O>[NH2:33][C@@H:32]1[C:31](=[O:43])[N:13]2[C:14]([C:15]([O:17][CH:18]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:16])=[C:9]([CH2:8][S:7][C:6]3[CH2:5][O:4][C:3](=[O:44])[C:2]=3[Cl:1])[CH2:10][S:11][C@H:12]12

Participants

7

Reactant 4

HCID 887MethanolHCID 79724-MethylmorpholineHCID 24819Phosphorus pentachlorideHCID 67908485HCID 67908485, compound

Product 1

HCID 67908473HCID 67908473, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

A stirred solution of diphenylmethyl 3-(3-chloro-2,5-dihydro-2-oxofuran-4-ylthiomethyl)-7β-phenylacetamidoceph-3-em-4-carboxylate (770 mg) in dichloromethane (10 ml) was cooled to -15° C. to -20° C., then N-methylmorpholine (0.263 ml) was added followed by a solution of phosphorus pentachloride in dichloromethane (9.3 ml of a solution containing 40 mg ml-1). The mixture was stirred at the same temperature for 0.5 h. Methanol (2.4 ml) was then added and the mixture stirred at room temperature for 0.5 h. Water (3.2 ml) was then added and the mixture vigorously stirred for a further 0.5 h. The dichloromethane was removed on a rotary evaporator and the residue partitioned between ethyl acetate and water. 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 (447 mg) was isolated by column chromatography using gradient elution (Kieselgel, 1:1 hexane:ethyl acetate going to neat ethyl acetate). υmax (CHCl3) 1775, 1625cm-1 ; δH(CDCl3), 1.77 (2H, br s), 3.43 (1H, d, J 18.16Hz), 3.63 (1H, d, J 18.12Hz), 3.94 (1H, d, J 12.98Hz), 4.05 (1H, d, J 12.93Hz), 4.51 (1H, d, J 16.20Hz), 4.60 (1H, d, J 16.17Hz), 4.81 (1H, d, J 5.11Hz), 4.97 (1H, d, J 5.11Hz), 6.98 (1H, s), 7.25-7.45 (10H, m).

Workup

  1. stirringthe mixture stirred at room temperature for 0.5 h
  2. stirringthe mixture vigorously stirred for a further 0.5 h
  3. customThe dichloromethane was removed on a rotary evaporator
  4. customthe residue partitioned between ethyl acetate and water
  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-63efdb130f3d4e7ead1bb62257eee997
Source dataset
uspto-grants-1992_10
Patent number
US05158946

Reaction notes

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