2,2-Dimethylcyclohexan-1-one → 2-Isopropyl-3-carboethoxy-4-(4-fluorophenyl)-5,6,7,8-tetrahydro-8,8-dimethylquinoline

HRID 324882

반응식

HRID 324882 반응식
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:11][C:12]1([CH3:19])[CH2:17][CH2:16][CH2:15][CH2:14][C:13]1=O.[F:20][C:21]1[CH:26]=[CH:25][C:24]([CH:27]=[C:28]([C:32](=O)[CH:33]([CH3:35])[CH3:34])[C:29]([OH:31])=[O:30])=[CH:23][CH:22]=1.CC(OCC1C2C(=CC=CC=2)C(CO[C:58]([CH3:60])=O)=C2C=1C=CC=C2)=O.C([O-])(=O)C.[NH4+:65]>C1COCC1.C([O-])(=O)C.[Cu+2].C([O-])(=O)C.C(Cl)Cl.CCCCCC.C(OCC)(=O)C.CCCCCC>[CH:33]([C:32]1[C:28]([C:29]([O:31][CH2:58][CH3:60])=[O:30])=[C:27]([C:24]2[CH:25]=[CH:26][C:21]([F:20])=[CH:22][CH:23]=2)[C:14]2[CH2:15][CH2:16][CH2:17][C:12]([CH3:19])([CH3:11])[C:13]=2[N:65]=1)([CH3:35])[CH3:34]

참가 물질

10

반응물 5

HCID 1369292,2-Dimethylcyclohexan-1-oneHCID 517165Ammonium AcetateHCID 613145Acetic acid 10-acetoxymethyl-anthracen-9-ylmethyl esterHCID 2733832Lithium HexamethyldisilazideHCID 544250042-[(4-Fluorophenyl)methylene]-4-methyl-3-oxopentanoic Acid

생성물 1

HCID 220050562-Isopropyl-3-carboethoxy-4-(4-fluorophenyl)-5,6,7,8-tetrahydro-8,8-dimethylquinoline

시약·촉매·용매 4

HCID 8895Cupric acetate촉매HCID 8028Tetrahydrofuran용매HCID 21226206Ethyl acetate hexane용매HCID 21226440Methylenechloride Hexane용매

실험 절차

To a solution of lithium bis(trimethylsilyl)amide (1.0 M/THF, 2 eq. 13.6 mL) in THF (15 mL) was added 2,2-dimethylcyclohexanone (1.88 mL, 13.6 mmol) at −78° C. The reaction was stirred for 15 minutes, and then the intermediate obtained in Step A (3 g, 11.4 mmol) was added dropwise. The reaction was stirred overnight and allowed to warm to room temperature. To the crude product was added acetic add (19.4 mL), ammonium acetate (2.62 g, 34.0 mmol) and copper acetate (5.14 g, 28.3 mmol). The reaction mixture was heated at 100° C. and the THF was removed by distillation. The reaction was heated to 130° C. and allowed to reflux for 24 hours. Ethyl acetate (100 mL) was added and washed with sodium bicarbonate (2×30 mL), water (2×20 mL), brine (2×20 mL), dried with MgSO4, filtered, and concentrated to afford an oil. Flash chromatography (5% ethyl acetate/hexane) afforded a white solid (1.36, 3.7 mmol, 32%). 1H NMR (300 MHz, CDCl3): δ 7.17 (m, 2H), 7.08 (m, 2H), 3.98 (q, J=7.4 Hz, 2H), 3.03 (septet, J=7.0 Hz, 1H), 2.35 (t, J=5.9 Hz, 2H), 1.70 (m, 4H), 1.36 (s, 6H), 1.31 (d, J=4.1 Hz, 6H), 0.965 (t, J=7.4 Hz, 3H). FAB-MS: calculated for (C23H28FNO) 369, found 370 (M+H. mp 124-126° C. Rf=0.6 (50% CH2Cl2/hexane).

후처리

  1. stirringThe reaction was stirred overnight
  2. temperatureThe reaction mixture was heated at 100° C.
  3. customthe THF was removed by distillation
  4. temperatureThe reaction was heated to 130° C.
  5. temperatureto reflux for 24 hours
  6. additionEthyl acetate (100 mL) was added
  7. washwashed with sodium bicarbonate (2×30 mL), water (2×20 mL), brine (2×20 mL)
  8. dry with materialdried with MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto afford an oil

출처 및 근거

ORD 기록
ord-a17314e3a38d4910bbbeb42d193a90d5
출처 데이터셋
uspto-grants-2001_04
특허 번호
US06218431B1

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