Potassium Hydroxide → 7-(Ethyloxy)-6-[(1-methylethyl)sulfonyl]-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid

HRID 245208ノート

反応式

HRID 245208 の反応式
[CH2:1]([O:3][C:4]1[CH:13]=[C:12]2[C:7]([C:8]([C:37]([O:39]C)=[O:38])=[C:9]([CH2:24][N:25]3[CH2:30][CH2:29][CH:28]([N:31]4[CH2:36][CH2:35][O:34][CH2:33][CH2:32]4)[CH2:27][CH2:26]3)[C:10]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=3)=[N:11]2)=[CH:6][C:5]=1[S:41]([CH:44]([CH3:46])[CH3:45])(=[O:43])=[O:42])[CH3:2].[OH-].[K+]>CO.O>[CH2:1]([O:3][C:4]1[CH:13]=[C:12]2[C:7]([C:8]([C:37]([OH:39])=[O:38])=[C:9]([CH2:24][N:25]3[CH2:26][CH2:27][CH:28]([N:31]4[CH2:36][CH2:35][O:34][CH2:33][CH2:32]4)[CH2:29][CH2:30]3)[C:10]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:21])[F:22])[CH:15]=3)=[N:11]2)=[CH:6][C:5]=1[S:41]([CH:44]([CH3:45])[CH3:46])(=[O:43])=[O:42])[CH3:2]

参加物

5

反応物 2

HCID 14797Potassium HydroxideHCID 67418887Methyl 7-(ethyloxy)-6-[(1-methylethyl)sulfonyl]-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

生成物 1

HCID 674183257-(Ethyloxy)-6-[(1-methylethyl)sulfonyl]-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid収率 102.1%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 962Water溶媒

実験手順

A stirred suspension of methyl 7-(ethyloxy)-6-[(1-methylethyl)sulfonyl]-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1.3 g, 1.959 mmol) and potassium hydroxide (0.879 g, 15.67 mmol) in methanol (15 mL) and water (3.75 mL) was heated to reflux for 20 h. The mixture was cooled to room temperature, and the solvent was removed under reduced pressure. The resulting yellow oil was partitioned between water and methylene chloride and cooled in an ice bath. The pH was adjusted to ⅚ with 2N HCl and the organic phase was separated. The aqueous phase was extracted twice more with methylene chloride. The combined organic extracts were washed with brine, dried, and concentrated to afford 7-(ethyloxy)-6-[(1-methylethyl)sulfonyl]-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (1.3 g, 97% yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ8.81 (s, 1H), 8.01 (s, 1H), 7.86-7.94 (m, 2H), 7.75-7.82 (m, 1H), 7.67 (s, 1H), 4.37 (q, J=6.80 Hz, 2H), 4.10 (br. s., 2H), 3.84 (quin, J=6.80 Hz, 1H), 3.56 (br. s., 4H), 3.02 (d, J=11.08 Hz, 2H), 2.52-2.63 (m, 2H), 2.44 (br. s., 4H), 2.33 (br. s., 1H), 1.79 (d, J=12.34 Hz, 2H), 1.44 (t, J=6.92 Hz, 3H), 1.26-1.39 (m, 2H), 1.23 (s, 3H), 1.21 (s, 3H); MS (m/z) 650.2 (M+H+).

後処理

  1. temperaturewas heated
  2. temperatureto reflux for 20 h
  3. customthe solvent was removed under reduced pressure
  4. customThe resulting yellow oil was partitioned between water and methylene chloride
  5. temperaturecooled in an ice bath
  6. customthe organic phase was separated
  7. extractionThe aqueous phase was extracted twice more with methylene chloride
  8. washThe combined organic extracts were washed with brine
  9. customdried
  10. concentrationconcentrated

出典と根拠

ORDレコード
ord-b80fb62be907486db35fe5ccf84a0c60
出典データセット
uspto-grants-2014_02
特許番号
US08658636B2

反応ノート

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