Sodium hydride → 1-(4-(S),5-(S)-Bis-benzyloxy-6-(R)-benzyloxymethyl-3-(R)-hydroxy-tetrahydro-pyran-2-(R)-yl)-3-(S)-(5-chloro-2-methoxy-phenyl)-3-fluoro-6-trifluoromethyl-1,3-dihydro-indol-2-one

HRID 895805노트

반응식

HRID 895805 반응식
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:23][CH3:24])=[C:6]([C@@:8]2([F:22])[C:16]3[C:11](=[CH:12][C:13]([C:17]([F:20])([F:19])[F:18])=[CH:14][CH:15]=3)[NH:10][C:9]2=[O:21])[CH:7]=1.[H-].[Na+].[CH2:27]([O:34][C@H:35]1[C@H:40]([O:41][CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[C@@H:39]([CH2:49][O:50][CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[O:38][C@@H:37]2[O:58][C@H:36]12)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(=O)(O)[O-].[Na+]>O1CCCC1>[CH2:27]([O:34][C@@H:35]1[C@@H:40]([O:41][CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[C@@H:39]([CH2:49][O:50][CH2:51][C:52]2[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=2)[O:38][C@@H:37]([N:10]2[C:11]3[C:16](=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=3)[C@@:8]([C:6]3[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=3[O:23][CH3:24])([F:22])[C:9]2=[O:21])[C@@H:36]1[OH:58])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

참가 물질

6

반응물 4

HCID 24758Sodium hydrideHCID 214350Bms 204352HCID 516892Sodium BicarbonateHCID 100943411,2-Anhydro-3,4,6-tri-O-benzyl-alpha-D-glucopyranose

생성물 1

HCID 208124891-(4-(S),5-(S)-Bis-benzyloxy-6-(R)-benzyloxymethyl-3-(R)-hydroxy-tetrahydro-pyran-2-(R)-yl)-3-(S)-(5-chloro-2-methoxy-phenyl)-3-fluoro-6-trifluoromethyl-1,3-dihydro-indol-2-one

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

To a round bottom flask containing (S)-3-(5-chloro-2-methoxy-phenyl)-3-fluoro-6-trifluoromethyl-1,3-dihydro-indol-2-one ((S)-II) (0.200 g, 0.55 mmol) was added anhydrous tetrahydrofuran (3 mL) and 95% sodium hydride (0.018 g, 0.7 mmol). The yellow solution was allowed to stir at room temperature for 30 minutes. 1,2-Anhydro-3,4,6-tri-O-benzyl-α-D-glucopyranose (prepared by the method of Halcomb and Danishefsky J. Am. Chem. Soc. 1989, 111, 6661) (0.480 g, 1.1 mmol) was then dissolved in anhydrous tetrahydrofuran (2.5 mL) and added dropwise to the reaction mixture over 15 minutes. The reaction was allowed to stir at reflux overnight. Once complete, the reaction was cooled and then poured into saturated sodium bicarbonate. The solution was extracted with ethyl acetate (3×). The organic layer was washed with brine and then dried over anhydrous sodium sulfate. The crude mixture was purified via flash chromatography (silica gel, 30% ethyl acetate in hexanes). The title product was obtained as a yellow oil (0.287 g, 65%). 1H NMR (CDCl3, 400 MHz): δ 7.79 (dd, 1H, J=1.8 Hz, 0.68 Hz), 7.45 (s, 1H), 7.39-7.20 (m, 18H), 6.69 (dd, 1H, J=7.6 Hz, 1.1 Hz), 5.43 (d, 1H, J=9.5 Hz), 4.93 (m, 3H), 4.67 (m, 1H), 4.55 (dd, 2H, J=12.3 Hz, 5.7 Hz), 4.3 (ddd, 1H, J=4.9 Hz, 4.2 Hz), 3.87 (d, 1H, J=9.3 Hz), 3.79-3.70 (m, 4H), 3.42 (s, 3H), 2.54 (d, 1H, J=4.3 Hz).

후처리

  1. additionadded dropwise to the reaction mixture over 15 minutes
  2. stirringto stir
  3. temperatureat reflux overnight
  4. temperatureOnce complete, the reaction was cooled
  5. extractionThe solution was extracted with ethyl acetate (3×)
  6. washThe organic layer was washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe crude mixture was purified via flash chromatography (silica gel, 30% ethyl acetate in hexanes)

출처 및 근거

ORD 기록
ord-f2a42148bc984bb2bd64cd99f508a14e
출처 데이터셋
uspto-grants-2005_07
특허 번호
US06916937B2

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