Hydrochloric Acid → 1-(3-(5-(3-Chloro-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2-ethylbenzyl)azetidine-3-carboxylic acid

HRID 1942710노트

반응식

HRID 1942710 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:16][C:15]([C:17]3[C:18]([CH2:32][CH3:33])=[C:19]([CH2:23][N:24]4[CH2:27][CH:26]([C:28]([O:30]C)=[O:29])[CH2:25]4)[CH:20]=[CH:21][CH:22]=3)=[N:14][N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[OH-].[Na+].Cl>C(O)(C)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:16][C:15]([C:17]3[C:18]([CH2:32][CH3:33])=[C:19]([CH2:23][N:24]4[CH2:25][CH:26]([C:28]([OH:30])=[O:29])[CH2:27]4)[CH:20]=[CH:21][CH:22]=3)=[N:14][N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]

참가 물질

6

반응물 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 58494145HCID 58494145, 화합물

생성물 1

HCID 584940121-(3-(5-(3-Chloro-4-isopropoxyphenyl)-1,3,4-thiadiazol-2-yl)-2-ethylbenzyl)azetidine-3-carboxylic acid수율 19.1%

시약·촉매·용매 2

HCID 962Water용매HCID 3776Isopropanol용매

실험 절차

To a solution of crude methyl 1-{[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3,4-thiadiazol-2-yl)-2-ethylphenyl]methyl}-3-azetidinecarboxylate (D13) (54 mg) in isopropanol (3 mL) and water (3 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 (basic conditions) to give 1-{[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3,4-thiadiazol-2-yl)-2-ethylphenyl]methyl}-3-azetidinecarboxylic acid (E4) (10 mg) as a TFA salt (off-white solid). δH (DMSO-d6, 400 MHz): 1.09 (3H, t), 1.35 (6H, d), 2.89 (2H, m), 3.61 (2H, m), 4.28 (3H, br. s.), 4.53 (2H, m), 4.84 (1H, m), 7.38 (1H, d), 7.44 (1H, m), 7.58 (2H, m), 7.96 (1H, dd), 8.10 (1H, d), 13.06 (1H, br s). δF (DMSO-d6, 376 MHz): −73.4. MS (ES): C24H26ClN3O3S requires 471. found 472.1 (M+H+).

후처리

  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 (basic conditions)

출처 및 근거

ORD 기록
ord-1bd480bca3164327b1bdcfcddff01aa6
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08389508B2

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