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

HRID 324882

反応式

HRID 324882 の反応式
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]

参加物

10

反応物 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

生成物 1

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

試薬・触媒・溶媒 4

HCID 8895Cupric acetate触媒HCID 8028Tetrahydrofuran溶媒HCID 21226206Ethyl acetate hexane溶媒HCID 21226440Methylenechloride Hexane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-a17314e3a38d4910bbbeb42d193a90d5
出典データセット
uspto-grants-2001_04
特許番号
US06218431B1

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