Methanol → 4-methoxybenzyl (6R,7R)-7-amino-3-[(S)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylate

HRID 376569Notes

Reaction equation

HRID 376569 reaction equation
P(Cl)(Cl)(Cl)(Cl)Cl.C1(CC([NH:16][C@@H:17]2[C:41](=[O:42])[N:19]3[C:20]([C:29]([O:31][CH2:32][C:33]4[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=4)=[O:30])=[C:21]([CH:24]4[CH2:28][CH2:27][CH2:26][O:25]4)[CH2:22][S:23][C@H:18]23)=O)C=CC=CC=1.CN1CCOCC1.CO>ClCCl.O>[NH2:16][C@@H:17]1[C:41](=[O:42])[N:19]2[C:20]([C:29]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=3)=[O:30])=[C:21]([C@@H:24]3[CH2:28][CH2:27][CH2:26][O:25]3)[CH2:22][S:23][C@H:18]12

Participants

7

Reactant 4

HCID 887MethanolHCID 79724-MethylmorpholineHCID 24819Phosphorus pentachlorideHCID 110057194-methoxybenzyl (6R,7R)-7-phenylacetamido-3-[(RS)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylate

Product 1

HCID 538410264-methoxybenzyl (6R,7R)-7-amino-3-[(S)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylateYield 38%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-10 °C

Procedure

Phosphorus pentachloride (2.15g, 10.32mmol) in dichloromethane (108ml) was added to 4-methoxybenzyl (6R,7R)-7-phenylacetamido-3-[(RS)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylate (3.40g, 6.69mmol) and N-methylmorpholine (1.50 ml, 13.64mmol) in dichloromethane (30ml) at -25° C. The reaction was stirred at -10±5° C. for 45min., then methanol (14ml) was added, and stirring continued for 45min. at room temperature. Water (27ml) was then added, and the mixture vigorously stirred for a further 1h. The dichloromethane was evaporated in vacuo, the aqueous residue washed with diethyl ether, then adjusted to pH7 with ammonium hydroxide in the presence of ethyl acetate. The mixture was extracted with ethyl acetate (x2), dried and concentrated in vacuo. The residue was purified by chromatography on silica gel eluting with 50, 70, 80% ethyl acetate in hexane yielding 4-methoxybenzyl (6R,7R)-7-amino-3-[(S)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylate (980mg, 38%) as a yellow foam; vmax (CH2Cl2) 1777, 1721, 1613, 1516, 1152cm-1 ; δH (CDCl3, 250MHz) 1.53-1.71 (1H, m), 1.84-2.02 (4H, m, 2 exch.), 2.25-2.40 (1H, m), 3.31 and 3.60 (2H, ABq, J 18.5Hz), 3.78-3.98 (2H, m), 3.81 (3H, s), 4.72 (1H, d, J 5.0Hz), 4.86-4.93 (2H, m), 5.19 (2H, s), 6.88 (2H, d, J 8.6Hz), 7.33 (2H, d, J 8.6Hz). [Mass spectrum: M+ (390)].

Workup

  1. stirringstirring
  2. waitcontinued for 45min. at room temperature
  3. stirringthe mixture vigorously stirred for a further 1h
  4. customThe dichloromethane was evaporated in vacuo
  5. washthe aqueous residue washed with diethyl ether
  6. extractionThe mixture was extracted with ethyl acetate (x2)
  7. customdried
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by chromatography on silica gel eluting with 50, 70, 80% ethyl acetate in hexane

Sources & evidence

ORD record
ord-6ea9685daa264087b66e2c9b735aee52
Source dataset
uspto-grants-2000_02
Patent number
US06020329

Reaction notes

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