Methanol → Diphenylmethyl 7beta-Amino-3-(2,5-dihydro-2-oxofuran-4-ylmethyloxy)ceph-3-em-4-carboxylate

HRID 467382Notes

Reaction equation

HRID 467382 reaction equation
[O:1]=[C:2]1[CH:6]=[C:5]([CH2:7][O:8][C:9]2[CH2:10][S:11][C@@H:12]3[C@H:32]([NH:33]C(=O)CC4C=CC=CC=4)[C:31](=[O:43])[N:13]3[C:14]=2[C:15]([O:17][CH:18]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[CH2:4][O:3]1.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:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[O:16])=[C:9]([O:8][CH2:7][C:5]3[CH2:4][O:3][C:2](=[O:1])[CH:6]=3)[CH2:10][S:11][C@H:12]12

Participants

7

Reactant 4

HCID 887MethanolHCID 79724-MethylmorpholineHCID 24819Phosphorus pentachlorideHCID 67908619Diphenylmethyl 3-(2,5-dihydro-2-oxofuran-4-ylmethyl oxy)-7beta-phenylacetamidoceph-3-em-4-carboxylate

Product 1

HCID 67908486Diphenylmethyl 7beta-Amino-3-(2,5-dihydro-2-oxofuran-4-ylmethyloxy)ceph-3-em-4-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-20 °C

Procedure

Diphenylmethyl 3-(2,5-dihydro-2-oxofuran-4-ylmethyl oxy)-7β-phenylacetamidoceph-3-em-4-carboxylate (958 mg) was dissolved in dichloromethane (13 ml) whilst under an inert atmosphere. The solution was cooled to -20° C. before treating with N-methylmorpholine (352 μl) followed by a solution of phosphorous pentachloride in dichloromethane (12.5 ml of 40 mg ml-1 solution). After stirring for 30 min. at -20° C. the solution was treated with methanol (3.2 ml) and then allowed to warm to RT. After a further 30 min. water (4.3 ml) was added and the reaction was stirred vigorously for 60 min. Solvent was removed by evaporation in vacuo and the residue dissolved in ethyl acetate/water. The pH of the mixture was adjusted to 6.5 with 1.0M aqueous ammonia. Separation of the organic phase was followed by washing with water and brine before drying over anhydrous magnesium sulphate. Purification was accomplished by chromatography of the crude material on silica gel (Keiselgel) eluting with ethyl acetate. The title compound was finally isolated as a foam (565 mg). υmax (CH2Cl2) 1780, 1755 and 1730cm-1 ; δH(CDCl3) 3.34 (1H, d, J 17.7Hz), 3.54 (1H, d, J 17.7Hz), 4.51-4.58 (2H, m), 4.70 (2H, bs) 4.75 (1H, d, J 4.7Hz), 4.97 (1H, d, J 4.7Hz), 5.93 (1H, s), and 7.26-7.40 (10H, m). [Mass spectrum: FAB +ve ion (3NOBA/Na+) MNa+ 501].

Workup

  1. temperatureto warm to RT
  2. stirringthe reaction was stirred vigorously for 60 min
  3. customSolvent was removed by evaporation in vacuo
  4. dissolutionthe residue dissolved in ethyl acetate/water
  5. customSeparation of the organic phase
  6. washby washing with water and brine
  7. dry with materialbefore drying over anhydrous magnesium sulphate
  8. customPurification
  9. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-db98e1379050445c8ec20cda286c1ad9
Source dataset
uspto-grants-1992_10
Patent number
US05158946

Reaction notes

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