Sodium hydride → 1,1-Dimethylethyl 4-(1,2-dihydro-2-oxo-3-quinolinyl)-4-hydroxy-1-piperidinecarboxylate

HRID 501949

반응식

HRID 501949 반응식
Br[C:2]1[C:3](=[O:12])[NH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.[H-].[Na+].C([Li])(C)(C)C.[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][C:30](=[O:33])[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21]>O1CCCC1>[OH:33][C:30]1([C:2]2[C:3](=[O:12])[NH:4][C:5]3[C:10]([CH:11]=2)=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH2:29][CH2:28][N:27]([C:25]([O:24][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:26])[CH2:32][CH2:31]1

참가 물질

6

반응물 4

HCID 24758Sodium hydrideHCID 2683383-Bromoquinolin-2-olHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178418306HCID 178418306, 화합물

생성물 1

HCID 594243951,1-Dimethylethyl 4-(1,2-dihydro-2-oxo-3-quinolinyl)-4-hydroxy-1-piperidinecarboxylate

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
-78 °C

실험 절차

A flask was charged with 3-bromoquinolin-2(1H)-one (U.S. Pat. Appl. Publ. 2002, U.S. 2002099208 A1; Payack, J. F. et al. J. Org. Chem. 2005, 70, 1, 175.) (1.0 g, 4.46 mmol) and sodium hydride (118 mg, 4.91 mmol). The solids were dissolved in tetrahydrofuran (30 mL), stirred for 15 min, and cooled to −78° C. The solution was treated with tert-butyllithium (1.7 M in pentane, 5.25 mL, 8.93 mmol) and stirred for 1 h. To this was added N-tert-butoxycarbonyl-4-piperidone (889 mg, 1.0 equiv). The ice bath was removed and stirring continued for 1 h. The reaction was quenched by addition of saturated ammonium chloride. The reaction was diluted with diethyl ether, washed with water (2×), then brine, dried over magnesium sulfate, and concentrated. The resulting oil was triturated with diethyl ether to give a white solid which was filtered, washed with diethyl ether, and air dried to give 430 mg (28%) as a white powder. 1H-NMR (CDCl3, 500 MHz) δ 1.48 (s, 9H), 1.57 (bs, 2H), 1.87 (m, 2H), 2.13 (m, 2H), 3.37 (m, 2H), 4.06 (m, 2H), 7.28 (m, 2H), 7.53 (m, 2H), 7.60 (m, 1H), 7.69 (s, 1H). Mass spec.: 367.35 (MNa)+.

후처리

  1. stirringstirred for 1 h
  2. customThe ice bath was removed
  3. stirringstirring
  4. waitcontinued for 1 h
  5. customThe reaction was quenched by addition of saturated ammonium chloride
  6. additionThe reaction was diluted with diethyl ether
  7. washwashed with water (2×)
  8. dry with materialbrine, dried over magnesium sulfate
  9. concentrationconcentrated
  10. customThe resulting oil was triturated with diethyl ether
  11. customto give a white solid which
  12. filtrationwas filtered
  13. washwashed with diethyl ether, and air
  14. customdried
  15. customto give 430 mg (28%) as a white powder

출처 및 근거

ORD 기록
ord-d0ee950fe52344cbabb8d65a861ff4ef
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07772244B2

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