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

HRID 467372Notes

Reaction equation

HRID 467372 reaction equation
[O:1]=[C:2]1[C:6]([CH2:7][S: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])=[CH:5][CH2:4][O:3]1.CN1CCOCC1>ClCCl>[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]([S:8][CH2:7][C:6]3[C:2](=[O:1])[O:3][CH2:4][CH:5]=3)[CH2:10][S:11][C@H:12]12

Participants

4

Reactant 2

HCID 79724-MethylmorpholineHCID 67908629Diphenylmethyl 3-(2,5-dihydro-2-oxofuran-3-yl-methylthio)-7beta-phenylacetamidoceph-3-em-4-carboxylate

Product 1

HCID 67908447Diphenylmethyl 7beta-Amino-3-(2,5-dihydro-2-oxofuran-3-ylmethylthio)ceph-3-em-4-carboxylateYield 89.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-30 °C

Procedure

Diphenylmethyl 3-(2,5-dihydro-2-oxofuran-3-yl-methylthio)-7β-phenylacetamidoceph-3-em-4-carboxylate (0.83g) was dissolved in dichloromethane (11 ml) and treated with N-methylmorpholine (298μl). The atmosphere was purged with argon and the mixture cooled to -30° C. A solution of phosphorus pentachloride in dichloromethane (10.6 ml of 40 mg ml-1 solution) was added and the reaction stirred at approximately -20° C. for 30 min. Methanol (2.7 ml) was added and the reaction allowed to warm to room temperature. Water (3.6 ml) was then added and the mixture stirred vigorously for 45 min. Dichloromethane was removed using a rotary evaporator and the residue partitioned between ethyl acetate and water. The pH of the solution was adjusted to 6.0 with 1.0M aqueous ammonia before separating the organic phase, washing with water and brine, and finally drying over magnesium sulphate. Evaporation of solvent gave a residue which was purified by chromatography on silica gel (Keiselgel, 7:3 ethyl acetate:hexane) to give the title compound (600 mg). υmax (CH2Cl2) 1780 and 1760cmhu -1; δH (CDCl3) 2.04 (2H, bs) 3.44-3.73 (4H, m), 4.70 (2H, s), 4.77 (1H, d, J 5.0Hz), 4.96 (1H, d, J 4.9Hz), 6.96 (1H, s) 7.11 (1H, s), 7.27-7.46 (10H, m). [mass spectrum: +ve ion (Thioglycerol) MH+ 495].

Workup

  1. customThe atmosphere was purged with argon
  2. additionA solution of phosphorus pentachloride in dichloromethane (10.6 ml of 40 mg ml-1 solution) was added
  3. additionMethanol (2.7 ml) was added
  4. temperatureto warm to room temperature
  5. additionWater (3.6 ml) was then added
  6. stirringthe mixture stirred vigorously for 45 min
  7. customDichloromethane was removed
  8. customa rotary evaporator
  9. customthe residue partitioned between ethyl acetate and water
  10. custombefore separating the organic phase
  11. washwashing with water and brine
  12. dry with materialfinally drying over magnesium sulphate
  13. customEvaporation of solvent
  14. customgave a residue which
  15. customwas purified by chromatography on silica gel (Keiselgel, 7:3 ethyl acetate:hexane)

Sources & evidence

ORD record
ord-d3bd57635d954ab2abce011fdabac061
Source dataset
uspto-grants-1992_10
Patent number
US05158946

Reaction notes

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