Methanol → t-Butyl (6R,7R)-7-amino-3-[(4RS)-2-oxotetrahydrofuran-4-yl]ceph-3-em-4-carboxylate

HRID 6294

반응식

HRID 6294 반응식
P(Cl)(Cl)(Cl)(Cl)Cl.[O:7]=[C:8]1[CH2:12][CH:11]([C:13]2[CH2:14][S:15][C@@H:16]3[C@H:27]([NH:28]C(=O)COC4C=CC=CC=4)[C:26](=[O:39])[N:17]3[C:18]=2[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:10][O:9]1.CN1CCOCC1.CO>ClCCl.O>[NH2:28][C@@H:27]1[C:26](=[O:39])[N:17]2[C:18]([C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])=[C:13]([CH:11]3[CH2:10][O:9][C:8](=[O:7])[CH2:12]3)[CH2:14][S:15][C@H:16]12

참가 물질

7

반응물 4

HCID 887MethanolHCID 79724-MethylmorpholineHCID 24819Phosphorus pentachlorideHCID 53910961t-butyl (6R,7R)-3-[(4RS)-2-oxotetrahydrofuran-4-yl]-7-phenoxyacetamidoceph-3-em-4-carboxylate

생성물 1

HCID 53649045t-Butyl (6R,7R)-7-amino-3-[(4RS)-2-oxotetrahydrofuran-4-yl]ceph-3-em-4-carboxylate수율 29.4%

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매2회

실험 절차

A solution of phosphorous pentachloride (0.380 g, 1.8 mmol) in dichloromethane (9.5 ml) was added to t-butyl (6R,7R)-3-[(4RS)-2-oxotetrahydrofuran-4-yl]-7-phenoxyacetamidoceph-3-em-4-carboxylate (0.554 g, 1.2 mmol) and N-methylmorpholine (265 μh, 2.4 mmol) in dichloromethane (15 ml) at <-20° C. under argon. Stirred 0.5 h at -15°±5° C. then methanol (3.5 ml) added, stirred 0.75 h then water (10 ml) added and stirred vigorously 1 h. The dichloromethane was removed in vacuo. ethyl acetate added and the aqueous layer adjusted to pH7 with dilute ammonium hydroxide and extracted twice with ethyl acetate. The extracts were washed with brine, dried, concentrated and flash chromatographed on silica gel eluting with 40,50,60,70,75% ethyl acetate in hexane to provide the title compound as a foam (0.120 g, 29%): (Found: M+, 340.1113. C15H20N2O5S requires M, 340.1093); νmax (CH2Cl2) 1775, 1715, 1367, 1155 cm-1 ; δH (250 MHz, CDCl3) 1.54 (9H, s , 1.97 (2H, bs), 2.35-2.95 (2H, m), 3.26 and 3.49 3.28 and 3.49 (2H, 2ABq, J 17.7 Hz), 4.0-4.45 (3H, m), 4.77, 4.79 (1H, 2d, J 4.7 Hz), 4.93, 4.95 (1H, 2d, J 4.7 Hz).

후처리

  1. stirringstirred 0.75 h
  2. stirringstirred vigorously 1 h
  3. customThe dichloromethane was removed in vacuo
  4. additionethyl acetate added
  5. extractionextracted twice with ethyl acetate
  6. washThe extracts were washed with brine
  7. customdried
  8. concentrationconcentrated
  9. customflash chromatographed on silica gel eluting with 40,50,60,70,75% ethyl acetate in hexane

출처 및 근거

ORD 기록
ord-4d70e3eec3d34997a22908f6fa4984e9
출처 데이터셋
uspto-grants-1993_09
특허 번호
US05246926

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