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

HRID 1421784Notes

Reaction equation

HRID 1421784 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×

Conditions

Temperature
-10 °C

Procedure

Phosphorus pentachloride (1.538 g, 7.5 mmol) in dichloromethane (39 ml) was added to t-butyl(6R,7R)-7-phenoxyacetamido-3-[(RS)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylate (2.267 g, 4.9 mmol) and N-methylmorpholine (1.1 ml, 10 mmol) in dichloromethane (20 ml) at -25° C. The reaction was stirred at -10±5° C. for 0.75 h then methanol (10 ml) added all at once, stirred 0.75 h then water (20 ml) added and stirred vigorously for 1 h. 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 (0.431 g, 27%); (Found: M+, 326.1299. C15H22N2O4S requires M, 326.1300); νmax (CH2Cl2) 1777, 1716, 1158 and 1052 cm-1 ; δH (CDCl3, 250 MHz) 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, J18.4 Hz), 3.8-4.0(2H,m), 4.75 (1H, d, J5.0 Hz) and 4.9-5.0 (2H, m). Further elution with 60% ethyl acetate in hexane gave the more polar (R)-diastereoisomer (0.533 g, 33%); (Found: M+ 326.1299. C15H22N2O4S requires M, 326.1300) νmax (CH2Cl2) 1776, 1721, 1158 and 1052 cm-1 ; δH (CDCl3, 250 MHz) 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, J17.8 Hz) 3.8-4.0 (2H, m), 4.67 (1H, d, J5.0 Hz), 4.93 (1H, d, J5.0 Hz), 5.0-5.15 (1H, m).

Workup

  1. stirringstirred 0.75 h
  2. stirringstirred vigorously for 1 h
  3. customThe dichloromethane was evaporated in vacuo
  4. washthe aqueous residue washed with ether
  5. extractionThe mixture was extracted twice with ethyl acetate
  6. customthe extracts dried
  7. concentrationconcentrated
  8. customflash chromatographed on silica gel eluting with 30,40,50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-1e2959f352e04c56872070a79d1ee080
Source dataset
uspto-grants-2000_06
Patent number
US06077952

Reaction notes

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