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Acetic Acid → 1-{2-[5-Fluoro-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}-2-(methyloxy)phenyl]ethyl}-4-piperidinecarboxylic acid

HRID 1942726
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HRID 1942726 반응식
[F:1][C:2]1[CH:3]=[C:4]([C:13]2[S:14][C:15]([C:18]3[CH:23]=[CH:22][C:21]([O:24][CH:25]([CH3:27])[CH3:26])=[C:20]([C:28]([F:31])([F:30])[F:29])[CH:19]=3)=[N:16][N:17]=2)[C:5]([O:11][CH3:12])=[C:6]([CH2:8][CH:9]=O)[CH:7]=1.[NH:32]1[CH2:37][CH2:36][CH:35]([C:38]([O:40]CC)=[O:39])[CH2:34][CH2:33]1.CC(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.O>[F:1][C:2]1[CH:3]=[C:4]([C:13]2[S:14][C:15]([C:18]3[CH:23]=[CH:22][C:21]([O:24][CH:25]([CH3:27])[CH3:26])=[C:20]([C:28]([F:29])([F:30])[F:31])[CH:19]=3)=[N:16][N:17]=2)[C:5]([O:11][CH3:12])=[C:6]([CH2:8][CH2:9][N:32]2[CH2:33][CH2:34][CH:35]([C:38]([OH:40])=[O:39])[CH2:36][CH2:37]2)[CH:7]=1
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참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 70770Ethyl 4-piperidinecarboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 86659002[5-Fluoro-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}-2-(methyloxy)phenyl]acetaldehyde

생성물 1

HCID 545793731-{2-[5-Fluoro-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}-2-(methyloxy)phenyl]ethyl}-4-piperidinecarboxylic acid
수율 45%

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매

실험 절차

To a solution of [5-fluoro-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}-2-(methyloxy)phenyl]acetaldehyde (D35) (80 mg) and ethyl 4-piperidinecarboxylate (138 mg) in dichloromethane (DCM) (15 mL) stirred at room temperature was added AcOH (0.15 mL). The reaction mixture was stirred at room temperature for 10 min. Then sodium triacetoxyborohydride (74.6 mg) was added. Stirring continued for overnight. Water was added to quench the reaction, and DCM was removed by evaporation. The mixture was extracted by EA for 3 times. The combined organic solution was washed by brine, dried over anhydrous Na2SO4. The dried solution was filtered and concentrated. The residue was dissolved in isopropanol (10 mL) and water (10 mL), sodium hydroxide (50 mg) was added. Stirring continued for 2 h at room temperature. 1M HCl solution was added until PH=6˜7. Then iPrOH was removed by evaporation. The aqueous layer was extracted by EA/THF/MeCN for 3 times. The combined organic layers were concentrated, and purified by Mass Directed AutoPrep to give 1-{2-[5-fluoro-3-{5-[4-[(1-methylethyl)oxy]-3-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl}-2-(methyloxy)phenyl]ethyl}-4-piperidinecarboxylic acid (E13) (45 mg) as an off-white solid. δH (DMSO-d6, 400 MHz): 1.34 (6H, d), 1.57 (2H, m), 1.79 (2H, d), 2.06 (2H, t), 2.19 (1H, m), 2.58 (2H, t), 2.87 (4H, t), 3.80 (3H, s), 4.94 (1H, m), 7.45 (1H, dd), 7.51 (1H, d), 7.88 (1H, dd), 8.23 (1H, d), 8.29 (1H, dd). δF (DMSO-d6, 376 MHz): −117.4, −61.3. MS (ES): C27H29F4N3O4S requires 567. found 568.2 (M+H+).

후처리

  1. stirringStirring
  2. waitcontinued for overnight
  3. customto quench
  4. customthe reaction, and DCM
  5. customwas removed by evaporation
  6. extractionThe mixture was extracted by EA for 3 times
  7. washThe combined organic solution was washed by brine
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationThe dried solution was filtered
  10. concentrationconcentrated
  11. dissolutionThe residue was dissolved in isopropanol (10 mL)
  12. additionwater (10 mL), sodium hydroxide (50 mg) was added
  13. stirringStirring
  14. waitcontinued for 2 h at room temperature
  15. addition1M HCl solution was added until PH=6˜7
  16. customThen iPrOH was removed by evaporation
  17. extractionThe aqueous layer was extracted by EA/THF/MeCN for 3 times
  18. concentrationThe combined organic layers were concentrated
  19. custompurified by Mass Directed AutoPrep

출처 및 근거

ORD 기록
ord-ed77ce4d70634726b014442fd678cb4f
출처 데이터셋
uspto-grants-2013_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08389508B2

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