Hydrochloric Acid → 1-[(2-Ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}phenyl)methyl]-4-piperidinecarboxylic acid

HRID 1942708ノート

反応式

HRID 1942708 の反応式
[CH2:1]([C:3]1[C:8]([C:9]2[S:10][C:11]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH:21]([CH3:23])[CH3:22])=[C:16]([C:24]([F:27])([F:26])[F:25])[CH:15]=3)=[N:12][N:13]=2)=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:28][N:29]1[CH2:34][CH2:33][CH:32]([C:35]([O:37]CC)=[O:36])[CH2:31][CH2:30]1)[CH3:2].[OH-].[Na+].Cl>C(O)(C)C.O>[CH2:1]([C:3]1[C:8]([C:9]2[S:10][C:11]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH:21]([CH3:23])[CH3:22])=[C:16]([C:24]([F:27])([F:26])[F:25])[CH:15]=3)=[N:12][N:13]=2)=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:28][N:29]1[CH2:30][CH2:31][CH:32]([C:35]([OH:37])=[O:36])[CH2:33][CH2:34]1)[CH3:2]

参加物

6

反応物 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 66981714Ethyl 1-[(2-ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}phenyl)methyl]-4-piperidinecarboxylate

生成物 1

HCID 545789131-[(2-Ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}phenyl)methyl]-4-piperidinecarboxylic acid収率 40.5%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 3776Isopropanol溶媒

実験手順

To a solution of ethyl 1-[(2-ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}phenyl)methyl]-4-piperidinecarboxylate (D7) (130 mg) in isopropanol (5 mL) and water (5 mL) was added sodium hydroxide (50 mg). The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was neutralized with 2N HCl till pH ˜6.0. The mixture was extracted with EA/THF for 3 times. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate. The dried solution was concentrated and the residue was purified by Mass Directed AutoPrep to give 1-[(2-ethyl-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}phenyl)methyl]-4-piperidinecarboxylic acid (E1) (50 mg) as an off-white solid. δH (DMSO-d6, 400 MHz): 1.10 (3H, t), 1.33 (6H, d), 1.54 (2H, m), 1.77 (2H, m), 2.06 (2H, m), 2.22 (1H, m), 2.76 (2H, m), 2.91 (2H, m), 4.93 (1H, m), 7.34 (1H, m), 7.51 (3H, m), 8.23 (2H, m), 12.13 (1H, br s). δF (DMSO-d6, 376 MHz): −61.3. MS (ES): C27H39F3N3O3S requires 533. found 534.2 (M+H+).

後処理

  1. extractionThe mixture was extracted with EA/THF for 3 times
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationThe dried solution was concentrated
  5. customthe residue was purified by Mass Directed AutoPrep

出典と根拠

ORDレコード
ord-1b1dea38ee2b423491328214fcc0cb6e
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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