Methanol → t-Butyl (6R,7R)-7-Amino-3-(tetrahydrofuran-2-yl)ceph-3-em-4-carboxylate

HRID 376558Notes

Reaction equation

HRID 376558 reaction equation
P(Cl)(Cl)(Cl)(Cl)Cl.O(CC([NH:17][C@@H:18]1[C:37](=[O:38])[N:20]2[C:21]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[C:22]([CH:25]3[CH2:29][CH2:28][CH2:27][O:26]3)[CH2:23][S:24][C@H:19]12)=O)C1C=CC=CC=1.CN1CCOCC1.CO>ClCCl.O>[NH2:17][C@@H:18]1[C:37](=[O:38])[N:20]2[C:21]([C:30]([O:32][C:33]([CH3:34])([CH3:36])[CH3:35])=[O:31])=[C:22]([CH:25]3[CH2:29][CH2:28][CH2:27][O:26]3)[CH2:23][S:24][C@H:19]12

Participants

7

Reactant 4

HCID 887MethanolHCID 79724-MethylmorpholineHCID 24819Phosphorus pentachlorideHCID 10027286t-butyl(6R,7R)-7-phenoxyacetamido-3-[(RS)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylate

Product 1

HCID 54097811t-Butyl (6R,7R)-7-Amino-3-(tetrahydrofuran-2-yl)ceph-3-em-4-carboxylateYield 27%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

Phosphorus pentachloride (1.538g, 7.5mmol) in dichloromethane (39ml) was added to t-butyl(6R,7R)-7-phenoxyacetamido-3-[(RS)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylate (2.267g, 4.9mmol) and N-methylmorpholine (1.1ml, 10mmol) in dichloromethane (20ml) at -25° C. The reaction was stirred at -10±5° C. for 0.75h then methanol (10ml) added all at once, stirred 0.75h then water (20ml) added and stirred vigorously for 1h. The dichloromethane was evaporated in vacuo, the aqueous residue washed with ether then adjusted to pH7 with ammonium hydroxide in the presence of ethyl acetate. The mixture was extracted twice with ethyl acetate, the extracts dried, concentrated and flash chromatographed on silica gel eluting with 30,40,50% ethyl acetate in hexane to give the more mobile (S)-diastereoisomer of the title compound (0.431g, 27%); (Found: M+, 326.1299. C15H22N2O4S requires M, 326.1300); vmax (CH2Cl2) 1777, 1716, 1158 and 1052cm-1 ; δH (CDCl3, 250MHz) 1.52 (9H,s), 1.55-1.8 (1H, m), 1.85-2.05 (4H, m), 2.3-2.45 (1H, m), 3.30 and 3.59 (2H, ABq, J18.4Hz), 3.8-4.0(2H,m), 4.75 (1H, d, J5.0Hz) and 4.9-5.0 (2H, m). Further elution with 60% ethyl acetate in hexane gave the more polar (R)-diastereoisomer (0.533g, 33%); (Found: M+ 326.1299. C15H22N2O4S requires M, 326.1300) vmax (CH2Cl2) 1776, 1721, 1158 and 1052cm-1 ; δH (CDCl3, 250MHz) 1.41 (2H, bs), 1.54 (9H, s), 1.6-1.85 (1H, m), 1.9-2.05 (2H, m), 2.05-2.2 (1H, m), 3.40 and 3.55 (2H, ABq, J17.8Hz) 3.8-4.0 (2H, m), 4.67 (1H, d, J5.0Hz), 4.93 (1H, d, J5.0Hz), 5.0-5.15 (1H, m).

Workup

  1. customThe dichloromethane was evaporated in vacuo
  2. washthe aqueous residue washed with ether
  3. extractionThe mixture was extracted twice with ethyl acetate
  4. customthe extracts dried
  5. concentrationconcentrated
  6. customflash chromatographed on silica gel eluting with 30,40,50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-a3156c6348e448959fee2e4830ae4a74
Source dataset
uspto-grants-2000_02
Patent number
US06020329

Reaction notes

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