HCID 57195341, compound → HCID 53912245, compound

HRID 376588Notes

Reaction equation

HRID 376588 reaction equation
[NH2:1][C@@H:2]1[C:29](=[O:30])[N:4]2[C:5]([C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=3)=[O:18])=[C:6]([C@H:9]3[CH2:13][CH2:12][C@@H:11]([CH2:14][O:15][CH3:16])[O:10]3)[CH2:7][S:8][C@H:3]12>C(Cl)(Cl)Cl>[NH2:1][C@@H:2]1[C:29](=[O:30])[N:4]2[C:5]([C:17]([O:19][CH2:20][C:21]3[CH:22]=[CH:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=3)=[O:18])=[C:6]([CH:9]3[CH2:13][CH2:12][CH:11]([CH2:14][O:15][CH3:16])[O:10]3)[CH2:7][S:8][C@H:3]12

Participants

3

Reactant 1

HCID 57195341HCID 57195341, compound

Product 1

HCID 53912245HCID 53912245, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

A solution of 4-methoxybenzyl (6R,7R)-3-[(2RS,5SR)-5-methoxymethyltetrahydrofuran-2-yl]-7-phenoxyacetamidoceph-3-em-4-carboxylate (1.93g) in dichloromethane (25ml) was cooled to -15 to -20° C., N-methylmorpholine (0.75ml) was added followed by a solution of phosphorus pentachloride in dichloromethane (26.5ml of a solution containing 40mg.ml-1). The mixture was stirred at the same temperature for 0.5h and then methanol (6.8ml) was added and the mixture stirred at room temperature for 0.5h. Water (10ml) was then added and the mixture vigorously stirred for 0.5h. 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 is (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-methoxymethyltetrahydrofuran-2-yl]ceph-3-em-4-carboxylate (388mg); vmax (CHCl3) 3410, 1776 and 1725cm-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 4.99Hz), 4.90 (1H,d, J 4.97Hz) 4.96 (1H,t, J 8.23Hz) 5.17 (2H,s), 6.88 (2H,d, J 8.60Hz) and 7.33 (2H,d, J 8.61Hz). [Mass spectrum: M+ (434)]; 4-methoxybenzyl (6R,7R)-7-amino-3-[(2R,5S)-5-methoxymethyltetrahydrofuran-2-yl]ceph-3-em-4-carboxylate (305mg); vmax (CHCl3) 3409, 1776 and 1725cm-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 17.78Hz), 3.69 (1H, d, J 17.75Hz), 3.80 (3H, s), 4.00-4.17 (1H,m), 4.70 (1H, d, J 4.92Hz), 4.93 (1H, d, J 4.95Hz), 5.10-5.20 (1H, m), 5.18 (1H, d, J 11.88Hz), 5.24 (1H, d, J 11.89Hz), 6.88 (1H,d, J 8.65Hz) and 7.35 (1H, d, J 8.64Hz). [Mass spectrum: M+ (434)].

Sources & evidence

ORD record
ord-d68c62dd989c491a8d395d5f65000fe4
Source dataset
uspto-grants-2000_02
Patent number
US06020329

Reaction notes

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