4-(3-Bromo-5-chlorophenyl)morpholine → HCID 59631266、化合物

HRID 1431760ノート

反応式

HRID 1431760 の反応式
Br[C:2]1[CH:3]=[C:4]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.[F:15][C:16]1[CH:25]=[C:24]2[C:19]([C:20]([CH:33]=[O:34])=[C:21]([CH3:32])[C:22]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=3)=[N:23]2)=[CH:18][CH:17]=1>C1COCC1>[Cl:8][C:6]1[CH:7]=[C:2]([CH:33]([C:20]2[C:19]3[C:24](=[CH:25][C:16]([F:15])=[CH:17][CH:18]=3)[N:23]=[C:22]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=3)[C:21]=2[CH3:32])[OH:34])[CH:3]=[C:4]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[CH:5]=1

参加物

4

反応物 2

HCID 532170884-(3-Bromo-5-chlorophenyl)morpholineHCID 59631569HCID 59631569、化合物

生成物 1

HCID 59631266HCID 59631266、化合物

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

An oven-dried conical flask was charged with 4-(3-bromo-5-chlorophenyl)-morpholine (0.384 g, 1.390 mmol) and 1.0 mL THF. While this solution was stirring at −78° C. under nitrogen, 2.5M butyllithium hexanes (0.556 mL, 1.390 mmol) was added via syringe. This solution was stirred at −78° C. for 30 minutes. After this time a solution of 7-fluoro-3-methyl-2-(pyridin-2-yl)quinoline-4-carbaldehyde (0.074 g, 0.278 mmol) in 2.0 mL THF was added, and the reaction continued at −78° C. for 45 minutes. Upon completion, the reaction was quenched with satd aqueous ammonium chloride and concd. The resulting material was partitioned between EtOAc and water, and the organic phase was dried over magnesium sulfate and concd. The afforded crude product was purified by column chromatography (silica; 0-50% EtOAc in hexanes) to yield (3-chloro-5-(4-morpholinyl)phenyl)(7-fluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)methanol as a white amorphous solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.70 (1H, d), 8.35 (1H, m), 8.01 (1H, t), 7.83 (1H, s), 7.71 (1H, d), 7.51 (1H, m), 7.42 (1H, m), 6.97 (1H, s), 6.83 (1H, s), 6.64 (1H, d, J=4.5 Hz), 6.55 (1H, d), 6.51 (1H, s), 3.69 (4H, t, J=4.8 Hz), 3.08 (4H, d, J=3.9 Hz), 2.46 (3H, s). Mass Spectrum (ESI) m/e=464.0 (M+1).

後処理

  1. stirringThis solution was stirred at −78° C. for 30 minutes
  2. customUpon completion, the reaction was quenched with satd aqueous ammonium chloride and concd
  3. customThe resulting material was partitioned between EtOAc and water
  4. dry with materialthe organic phase was dried over magnesium sulfate and concd
  5. customThe afforded crude product
  6. customwas purified by column chromatography (silica; 0-50% EtOAc in hexanes)

出典と根拠

ORDレコード
ord-ae3f3798d0184943b8a40231a990dbe7
出典データセット
uspto-grants-2015_01
特許番号
US08940724B2

反応ノート

読み込み中…