Methanol → HCID 131721639, compound

HRID 376616Notes

Reaction equation

HRID 376616 reaction equation
C1(CC([NH:10][C@@H:11]2[C:36](=[O:37])[N:13]3[C:14]([C:24]([O:26][CH2:27][C:28]4[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=4)=[O:25])=[C:15]([CH:18]4[CH:22]([CH3:23])[CH2:21][CH2:20][O:19]4)[CH2:16][S:17][C@H:12]23)=O)C=CC=CC=1.CN1CCOCC1.P(Cl)(Cl)(Cl)(Cl)Cl.CO>ClCCl.O>[NH2:10][C@@H:11]1[C:36](=[O:37])[N:13]2[C:14]([C:24]([O:26][CH2:27][C:28]3[CH:29]=[CH:30][C:31]([O:34][CH3:35])=[CH:32][CH:33]=3)=[O:25])=[C:15]([CH:18]3[CH:22]([CH3:23])[CH2:21][CH2:20][O:19]3)[CH2:16][S:17][C@H:12]12

Participants

7

Reactant 4

HCID 887MethanolHCID 79724-MethylmorpholineHCID 24819Phosphorus pentachlorideHCID 131721640HCID 131721640, compound

Product 1

HCID 131721639HCID 131721639, compoundYield 37%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-5 °C

Procedure

4-Methoxybenzyl (6R, 7R) -7-phenylacetamido-3-[(2RS,3SR)-3-methyltetrahydrofuran-2-yl]ceph-3-em-4-carboxylate (0.692g) in dry dichloromethane (5ml) under argon was cooled to -20° C. This solution was then treated with 4-methylmorpholine (0.268g, 0.291ml) followed by a solution of phosphorus pentachloride in dichloromethane (0.415g in 10.37ml) in a rapid dropwise fashion. The solution was allowed to warm to -5° C. and maintained at this temperature for 0.5h. Methanol (5ml) was then added in one portion and the solution allowed to warm to room temperature, and stirred for 0.5h. Water (5ml) was then added and the solution rapidly stirred for a further 0.75h. The dichloromethane was evaporated at reduced pressure and replaced with ethyl acetate. The pH was adjusted to 7.5 with aqueous 880 ammonia. The aqueous phase was extracted with ethyl acetate and the combined organic layers washed with brine and dried. Removal of solvent and column chromatography on silica gel eluting with 60 and then 70% ethyl acetate in hexane afforded the (2S,3R) isomer of the title compound as a pale yellow foam, (0.197g, 37%); vmax (CH2Cl2) 1777, 1720 and 1613cm-1 ; δH (CDCl3) 0.89 (3H, d, J 7.2Hz), 1.56 (1H, m), 2.14 (1H, m), 2.73 (1H, m), 3.37 and 3.57 (2H, ABq, J 18.0Hz), 3.73 (1H, m), 3.82 (3H, s), 4.05 (1H, m), 4.79 (1H, d, J 4.8Hz), 4.93 (1H, d, 4.8Hz), 4.98 (1H, d, J 7.6Hz), 5.17 (2H, s), 6.88 (2H, d, J 8.6Hz) and 7.33 (2H, d, J 8.6Hz). [Mass spectrum: +ve ion (3-nitrobenzyl alcohol, sodium acetate) MH+ (405), MNa+ (427)].

Workup

  1. temperaturemaintained at this temperature for 0.5h
  2. temperatureto warm to room temperature
  3. stirringthe solution rapidly stirred for a further 0.75h
  4. customThe dichloromethane was evaporated at reduced pressure
  5. extractionThe aqueous phase was extracted with ethyl acetate
  6. washthe combined organic layers washed with brine
  7. customdried
  8. customRemoval of solvent and column chromatography on silica gel eluting with 60

Sources & evidence

ORD record
ord-e25827cce9a94fa6820ee190462fb830
Source dataset
uspto-grants-2000_02
Patent number
US06020329

Reaction notes

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