Water → 2-(3-cyano-2-cyclohexyl-5-methyl-4-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrol-1-yl)acetic acid

HRID 1189534ノート

反応式

HRID 1189534 の反応式
[C:1]([C:3]1[C:7]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[S:15]([N:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)(=[O:17])=[O:16])=[C:6]([CH3:23])[N:5]([CH2:24][C:25]([O:27]CC)=[O:26])[C:4]=1[CH:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1)#[N:2].O.O.[OH-].[Li+]>O1CCCC1>[C:1]([C:3]1[C:7]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[S:15]([N:18]2[CH2:19][CH2:20][CH2:21][CH2:22]2)(=[O:17])=[O:16])=[C:6]([CH3:23])[N:5]([CH2:24][C:25]([OH:27])=[O:26])[C:4]=1[CH:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1)#[N:2]

参加物

5

反応物 3

HCID 962WaterHCID 168937Lithium hydroxide, monohydrate2 回HCID 53247599ethyl 2-(3-cyano-2-cyclohexyl-5-methyl-4-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrol-1-yl)acetate

生成物 1

HCID 532476002-(3-cyano-2-cyclohexyl-5-methyl-4-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrol-1-yl)acetic acid収率 97%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of ethyl 2-(3-cyano-2-cyclohexyl-5-methyl-4-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrol-1-yl)acetate (485 mg, 0.975 mmol) in tetrahydrofuran (2.9 mL), and water (0.98 mL), was added solid lithium hydroxide monohydrate (40.9 mg, 0.975 mmol). The reaction was stirred at room temperature for 45 minutes, after which analysis by LCMS indicated that the reaction was not complete. After 20 more minutes, an additional equivalent of lithium hydroxide monohydrate (40.9 mg) was added, and the reaction was stirred at room temperature for an additional 20 minutes, after which it was determined to be complete by LCMS analysis. Concentration of the reaction mixture, followed by acidification with aqueous 3M hydrochloric acid solution (0.65 mL), extraction with dichloromethane (1×50 mL), then ethyl acetate (2×50 mL), drying (sodium sulfate), filtering and concentration afforded 2-(3-cyano-2-cyclohexyl-5-methyl-4-(2-(pyrrolidin-1-ylsulfonyl)benzyl)-1H-pyrrol-1-yl)acetic acid (442 mg, 0.941 mmol, 97% yield). 1H NMR (400 MHz, CDCl3) δ (ppm) 7.96 (d, 1H), 7.43 (app. t, 1H), 7.32 (dd, 1H), 7.04 (d, 1H), 4.57 (s, 2H), 4.29 (s, 2H), 3.33-3.36 (m, 4H), 2.50 (m, 1H), 1.93-1.96 (m, 7H), 1.70-1.88 (m, 8H), 1.28-1.32 (m, 2H).

後処理

  1. stirringthe reaction was stirred at room temperature for an additional 20 minutes
  2. extractionConcentration of the reaction mixture, followed by acidification with aqueous 3M hydrochloric acid solution (0.65 mL), extraction with dichloromethane (1×50 mL)
  3. dry with materialethyl acetate (2×50 mL), drying (sodium sulfate)
  4. filtrationfiltering
  5. concentrationconcentration

出典と根拠

ORDレコード
ord-862ffa70b9db42728cb00087026e7064
出典データセット
uspto-grants-2014_03
特許番号
US08674115B2

反応ノート

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