Potassium Hydroxide → 6-(4-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)piperidin-1-yl)-1-methyl-1H-indole-3-carboxylic acid

HRID 1689813ノート

反応式

HRID 1689813 の反応式
C[O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([N:14]3[CH2:19][CH2:18][CH:17]([O:20][CH2:21][C:22]4[C:23]([C:30]5[C:35]([Cl:36])=[CH:34][CH:33]=[CH:32][C:31]=5[Cl:37])=[N:24][O:25][C:26]=4[CH:27]4[CH2:29][CH2:28]4)[CH2:16][CH2:15]3)=[CH:11][CH:12]=2)[N:7]([CH3:38])[CH:6]=1)=[O:4].[OH-].[K+]>CO.C1COCC1.O1CCOCC1>[CH:27]1([C:26]2[O:25][N:24]=[C:23]([C:30]3[C:31]([Cl:37])=[CH:32][CH:33]=[CH:34][C:35]=3[Cl:36])[C:22]=2[CH2:21][O:20][CH:17]2[CH2:18][CH2:19][N:14]([C:10]3[CH:9]=[C:8]4[C:13]([C:5]([C:3]([OH:4])=[O:2])=[CH:6][N:7]4[CH3:38])=[CH:12][CH:11]=3)[CH2:15][CH2:16]2)[CH2:28][CH2:29]1

参加物

6

反応物 2

HCID 14797Potassium HydroxideHCID 593693306-{4-[5-Cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-ylmethoxy]-piperidin-1-yl}-1-methyl-1H-indole-3-carboxylic acid methyl ester

生成物 1

HCID 252047676-(4-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)piperidin-1-yl)-1-methyl-1H-indole-3-carboxylic acid

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
70 °C

実験手順

In a 500 mL round bottom flask under nitrogen, containing a solution of 9 g (16.23 mmol) of 6-{4-[5-cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-ylmethoxy]-piperidin-1-yl}-1-methyl-1H-indole-3-carboxylic acid methyl ester in 80 mL of methanol, 80 mL of THF and 30 mL dioxane, is added 2N KOH (40 mL, 81.16 mmol). The reaction mixture is stirred at 70° C. overnight. The reaction mixture is then cooled to room temperature, and the solvent removed under vacuum. The residue is diluted with 100 mL of water, and washed with MTBE. The aqueous layer is acidified (pH 5) by addition of 2N HCl, then, it is extracted with CH2Cl2 (3×150 mL). The organics are dried over MgSO4, filtered, and evaporated to yield a light green solid that is recrystallized from MeOH/CH3CN (6.05 g (70%)). MS (m/e): 540 (M+1).

後処理

  1. temperatureThe reaction mixture is then cooled to room temperature
  2. customthe solvent removed under vacuum
  3. additionThe residue is diluted with 100 mL of water
  4. washwashed with MTBE
  5. additionby addition of 2N HCl
  6. extractionit is extracted with CH2Cl2 (3×150 mL)
  7. dry with materialThe organics are dried over MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. customto yield a light green solid that
  11. customis recrystallized from MeOH/CH3CN (6.05 g (70%))

出典と根拠

ORDレコード
ord-2eae1537a4bd48c699d3ffbe01af1ec8
出典データセット
uspto-grants-2012_04
特許番号
US08153624B2

反応ノート

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