Isopropanol → (4aR,6R,8aS)-2-(benzoylamino)-8a-(5-bromo-2-fluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazine-6-carboxylic acid

HRID 68416

반응식

HRID 68416 반응식
O.C[N+]1([O-])CC[O:6]CC1.[Br:10][C:11]1[CH:12]=[CH:13][C:14]([F:38])=[C:15]([C@:17]23[CH2:26][O:25][C@@H:24]([CH2:27][OH:28])[CH2:23][C@H:22]2[CH2:21][S:20][C:19]([NH:29][C:30](=[O:37])[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[N:18]3)[CH:16]=1.CC(O)C>C(#N)C.[Ru]([O-])(=O)(=O)=O.C([N+](CCC)(CCC)CCC)CC>[C:30]([NH:29][C:19]1[S:20][CH2:21][C@@H:22]2[CH2:23][C@H:24]([C:27]([OH:6])=[O:28])[O:25][CH2:26][C@:17]2([C:15]2[CH:16]=[C:11]([Br:10])[CH:12]=[CH:13][C:14]=2[F:38])[N:18]=1)(=[O:37])[C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1

참가 물질

6

반응물 3

HCID 3776IsopropanolHCID 2724197N-Methylmorpholine N-oxide monohydrateHCID 86762652N-[(4aR,6R,8aS)-8a-(5-bromo-2-fluorophenyl)-6-(hydroxymethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

생성물 1

HCID 86762653(4aR,6R,8aS)-2-(benzoylamino)-8a-(5-bromo-2-fluorophenyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazine-6-carboxylic acid수율 113.7%

시약·촉매·용매 2

HCID 178419074HCID 178419074, 화합물촉매HCID 6342Acetonitrile용매

실험 절차

N-Methylmorpholine N-oxide monohydrate (3.38 g, 25.0 mmol) and tetrapropylammonium perruthenate (0.147 g, 0.417 mmol) were added to a solution of N-[(4aR,6R,8aS)-8a-(5-bromo-2-fluorophenyl)-6-(hydroxymethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C33) (2.0 g, 4.17 mmol) in acetonitrile (75 mL). The reaction mixture was allowed to stir at room temperature for 16 hours. 2-Propanol (200 mL) was added to the reaction mixture and the resulting solution was left stirring at room temperature for 35 minutes. After that time, the reaction mixture was concentrated under reduced pressure. The oily residue was partitioned between aqueous 0.25 M sodium hydroxide (200 mL) and a 1:1 solution of diethyl ether:ethyl acetate (200 mL each). The layers were isolated and the organic layer was washed with aqueous 0.25 M sodium hydroxide (3×200 mL). The combined aqueous layers were then acidified to pH 1 with 2 M aqueous hydrochloric acid (300 mL). The now heterogeneous mixture was extracted with ethyl acetate (4×200 mL). The combined organics were then dried over sodium sulfate, filtered and concentrated under reduced pressure to give the product (2.34 g) as a purple solid, which was taken directly to the following step. LCMS m/z 495.1 [M+H+]. 1H NMR (400 MHz, CD3OD) δ 8.08-8.11 (m, 1H), 7.50-7.64 (m, 4H), 7.17-7.22 (m, 1H), 4.39 (dd, J=11.8, 2.8 Hz, 1H), 4.20 (d, J=12.1 Hz, 1H), 4.04-4.07 (m, 1H), 3.06 (dd, J=12.9, 4.3 Hz, 1H), 2.92 (dd, J=13.7, 3.1 Hz, 1H), 2.13-2.18 (m, 1H), 2.05-2.09 (m, 1H), 1.99-2.02 (m, 4H).

후처리

  1. waitthe resulting solution was left
  2. stirringstirring at room temperature for 35 minutes
  3. concentrationAfter that time, the reaction mixture was concentrated under reduced pressure
  4. customThe oily residue was partitioned between aqueous 0.25 M sodium hydroxide (200 mL)
  5. customThe layers were isolated
  6. washthe organic layer was washed with aqueous 0.25 M sodium hydroxide (3×200 mL)
  7. extractionThe now heterogeneous mixture was extracted with ethyl acetate (4×200 mL)
  8. dry with materialThe combined organics were then dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-03cebc98b9304977888f21fadd8b1ee8
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822456B2

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