Sodium Hydroxide → 1-{2-[3-(2-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylic acid

HRID 1942745ノート

反応式

HRID 1942745 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:13][C:14]([C:17]3[C:18]([CH2:36][CH3:37])=[C:19]([CH2:23][CH2:24][N:25]4[CH2:30][CH2:29][CH:28]([C:31]([O:33]CC)=[O:32])[CH2:27][CH2:26]4)[CH:20]=[CH:21][CH:22]=3)=[CH:15][N:16]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[OH-].[Na+]>C(O)(C)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:13][C:14]([C:17]3[C:18]([CH2:36][CH3:37])=[C:19]([CH2:23][CH2:24][N:25]4[CH2:26][CH2:27][CH:28]([C:31]([OH:33])=[O:32])[CH2:29][CH2:30]4)[CH:20]=[CH:21][CH:22]=3)=[CH:15][N:16]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]

参加物

5

反応物 2

HCID 14798Sodium HydroxideHCID 58494013Ethyl 1-{2-[3-(2-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylate

生成物 1

HCID 545771561-{2-[3-(2-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylic acid収率 15.8%

試薬・触媒・溶媒 2

HCID 962Water溶媒2 回HCID 3776Isopropanol溶媒

実験手順

To a solution of ethyl 1-{2-[3-(2-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylate (D89) (120 mg) in isopropanol (40 mL) and water (10 mL) stirred under nitrogen at room temperature was added a solution of NaOH (17.7 mg) in water in one charge. The reaction mixture was stirred at room temperature overnight. Isopropanol was removed in vacuo. The residue was dissolved in water and acidified with 1N HCl to pH=5. The solvent was removed in vacuo, the residue was dissolved in THF, and filtered. The filtrate was purified by Mass Directed AutoPrep to give 1-{2-[3-(2-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3-thiazol-5-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylic acid (E40) (18 mg) as a TFA salt (white solid). δH (DMSO-d6, 400 MHz): 1.11 (3H, t), 1.34 (6H, d), 1.76 (2H, m), 2.11 (2H, m), 2.71 (2H, m), 3.07 (4H, m), 3.27 (2H, m), 3.53 (1H, m), 3.67 (2H, m), 4.80 (1H, m), 7.33 (4H, m), 7.82 (1H, s), 7.87 (1H, dd), 7.99 (1H, d), 9.29 (1H, br s), 12.59 (1H, br s). δF (DMSO-d6, 376 MHz): −73.5. MS (ES): C28H33ClN2O3S requires 512. found 513.1 (M+H+).

後処理

  1. additioncharge
  2. customIsopropanol was removed in vacuo
  3. dissolutionThe residue was dissolved in water
  4. customThe solvent was removed in vacuo
  5. dissolutionthe residue was dissolved in THF
  6. filtrationfiltered
  7. customThe filtrate was purified by Mass Directed AutoPrep

出典と根拠

ORDレコード
ord-13e9f1f472104c9c8ccdec42f98916fb
出典データセット
uspto-grants-2013_03
特許番号
US08389508B2

反応ノート

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