Hydrochloric Acid → (2Z)-3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]-2-propenoic acid

HRID 1512897ノート

反応式

HRID 1512897 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:18]=[CH:19][CH:20]=[C:21]4[C:25]=3[N:24]([CH3:26])[CH:23]=[C:22]4/[CH:27]=[CH:28]\[C:29]([O:31]C)=[O:30])[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[OH-].[Na+].Cl>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:18]=[CH:19][CH:20]=[C:21]4[C:25]=3[N:24]([CH3:26])[CH:23]=[C:22]4/[CH:27]=[CH:28]\[C:29]([OH:31])=[O:30])[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:10])[CH3:11]

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 59146121HCID 59146121、化合物

生成物 1

HCID 59146033(2Z)-3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]-2-propenoic acid収率 86%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
60 °C

実験手順

To a solution of methyl (2Z)-3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]-2-propenoate (D63) (30 mg) in THF (5 mL) was added aqueous NaOH (2 M, 1 mL). The reaction was stirred at 60° C. for 4 h. The mixture was cooled to room temperature and acidified with aqueous HCl (2 M) to pH 4-5, partitioned between ethyl acetate (25 mL) and water (25 mL). The organic phase was washed with water (25 mL), dried over anhydrous sodium sulphate and evaporated to give the crude product, which was purified by Mass Directed Auto Prep to afford (2Z)-3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]-2-propenoic acid (E38) (25 mg). δH (DMSO-d6, 400 MHz): 1.36 (6H, d), 3.75 (3H, s), 4.89 (1H, m), 5.77 (1H, d), 7.34 (2H, m), 7.45 (1H, d), 7.52 (1H, dd), 8.07 (1H, dd), 8.14 (1H, dd), 8.21 (1H, d), 8.70 (1H, s), 12.02 (1H, br s). MS (ES): C23H20ClN3O4 requires 437; found 438.2 (M+H+).

後処理

  1. temperatureThe mixture was cooled to room temperature
  2. custompartitioned between ethyl acetate (25 mL) and water (25 mL)
  3. washThe organic phase was washed with water (25 mL)
  4. dry with materialdried over anhydrous sodium sulphate
  5. customevaporated
  6. customto give the crude product, which
  7. customwas purified by Mass Directed Auto Prep

出典と根拠

ORDレコード
ord-cf2c2d72491549d2ab247bdb7aa34a22
出典データセット
uspto-grants-2012_07
特許番号
US08217028B2

反応ノート

読み込み中…