Methanol → HCID 131721505, compound

HRID 1421811Notes

Reaction equation

HRID 1421811 reaction equation
COC[CH:4]1[O:8][CH:7]([C:9]2[CH2:10][S:11][C@@H:12]3[C@H:28]([NH:29]C(=O)COC4C=CC=CC=4)[C:27](=[O:40])[N:13]3[C:14]=2[C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)=[O:16])[CH2:6][CH2:5]1.CN1CC[O:45][CH2:44]C1.P(Cl)(Cl)(Cl)(Cl)Cl.[CH3:54]O>ClCCl.O>[NH2:29][C@@H:28]1[C:27](=[O:40])[N:13]2[C:14]([C:15]([O:17][CH2:18][C:19]3[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=3)=[O:16])=[C:9]([C@:7]3([CH3:54])[CH2:6][CH2:5][C@H:4]([O:45][CH3:44])[O:8]3)[CH2:10][S:11][C@H:12]12

Participants

7

Reactant 4

HCID 887MethanolHCID 79724-MethylmorpholineHCID 24819Phosphorus pentachlorideHCID 131721506HCID 131721506, compound

Product 1

HCID 131721505HCID 131721505, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of 4-methoxybenzyl (6R,7R)-3-[(2RS,5SR)-5-methoxymethyltetrahydrofuran-2-yl]-7-phenoxyacetamidoceph-3-em-4-carboxylate (1.93 g) in dichloromethane (25 ml) was cooled to -15 to -20° C., N-methylmorpholine (0.75 ml) was added followed by a solution of phosphorus pentachloride in dichloromethane (26.5 ml of a solution containing 40 mg·ml-1). The mixture was stirred at the same temperature for 0-5 h and then methanol (6.8 ml) was added and the mixture stirred at room temperature for 0.5 h. Water (10 ml) was then added and the mixture vigorously stirred for 0.5 h. The dichloromethane was then removed on a rotary evaporator and the residue was partitioned between ether and water. The aqueous phase was stirred with ethyl acetate and the pH was adjusted to 6.2 with 1N aqueous ammonia. The organic phase was washed with water and brine, dried over magnesium sulphate and evaporated. The products were separated by column chromatography of the residue using gradient elution (silica gel, 1:1 hexane:ethyl acetate going to neat ethyl acetate). The following were obtained in order of elution 4-methoxybenzyl (6R,7R)-7-amino-3-[(2S,5R)-5-methoxy-methyltetrahydrofuran-2-yl]ceph-3-em-4-carboxylate (388 mg); νmax (CHCl3) 3410, 1776 and 1725 cm-1 ; δH (CDCl3) 1.59-1.78 (2H,m), 1.93-2.08 (1H,m), 2.18-2.32 (1H,m), 2.54 (2H, br s), 3.33-3.54 (3H,m), 3.38 (3H,s), 3.80 (3H,s), 4.00-4.11 (1H,m), 4.76 (1H,d, J 4.99 Hz), 4.90 (1H,d, J 4.97 Hz) 4.96 (1H,t, J 8.23 Hz) 5.17 (2H,s), 6.88 (2H,d, J 8.60 Hz) and 7.33 (2H,d, J 8.61 Hz). [Mass spectrum: M+ (434)]; 4-methoxybenzyl (6R,7R)-7-amino-3-[(2R,5S)-5-methoxymethyltetrahydrofuran-2-yl]ceph-3-em-4-carboxylate (305 mg); νmax (CHCl3) 3409, 1776 and 1725 cm-1 ; δH (CDCl3) 1.60-1.81 (2H, m), 1.85-2.01 (2H, m), 3.30-3.50 (2H, m), 3.38 (3H, s), 3.44 (1H,d, J 17.78 Hz), 3.69 (1H, d, J 17.75 Hz), 3.80 (3H, s), 4.00-4.17 (1H,m), 4.70 (1H, d, J 4.92 Hz), 4.93 (1H, d, J 4.95 Hz), 5.10-5.20 (1H, m), 5.18 (1H, d, J 11.88 Hz), 5.24 (1H, d, J 11.89 Hz), 6.88 (1H,d, J 8.65 Hz) and 7.35 (1H, d, J 8.64 Hz). [Mass spectrum: M+ (434)].

Workup

  1. stirringthe mixture stirred at room temperature for 0.5 h
  2. stirringthe mixture vigorously stirred for 0.5 h
  3. customThe dichloromethane was then removed on a rotary evaporator
  4. customthe residue was partitioned between ether and water
  5. stirringThe aqueous phase was stirred with ethyl acetate
  6. washThe organic phase was washed with water and brine
  7. dry with materialdried over magnesium sulphate
  8. customevaporated
  9. customThe products were separated by column chromatography of the residue
  10. washelution (silica gel, 1:1 hexane:ethyl acetate going to neat ethyl acetate)

Sources & evidence

ORD record
ord-847c12ba1cd3440890cbc3ce687de076
Source dataset
uspto-grants-2000_06
Patent number
US06077952

Reaction notes

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