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Sodium Hydroxide → 1-{[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]methyl}-4-piperidinecarboxylic acid

HRID 1512916
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HRID 1512916 반응식
[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[CH2:27][N:28]3[CH2:33][CH2:32][CH:31]([C:34]([O:36]CC)=[O:35])[CH2:30][CH2:29]3)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[OH-].[Na+]>O1CCCC1.C(O)C.O>[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[CH2:27][N:28]3[CH2:33][CH2:32][CH:31]([C:34]([OH:36])=[O:35])[CH2:30][CH2:29]3)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]
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참가 물질

6

반응물 2

HCID 14798Sodium HydroxideHCID 59146087Ethyl 1-{[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]methyl}-4-piperidinecarboxylate

생성물 1

HCID 445487341-{[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]methyl}-4-piperidinecarboxylic acid수율 48%

시약·촉매·용매 3

HCID 702Ethanol용매
HCID 962
Water
용매
HCID 8028Tetrahydrofuran용매

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온도
20 °C

실험 절차

To a solution of ethyl 1-{[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]methyl}-4-piperidinecarboxylate (D79) (308 mg) in tetrahydrofuran (5 mL) and ethanol (5 mL) stirred at 20° C. was added a solution of sodium hydroxide (60 mg) in water (5 mL) in one charge. The reaction mixture was stirred at 20° C. overnight. The reaction mixture was concentrated and then H2SO4 (0.1 M) solution was added dropwise until no further white precipitate was formed. The solid was filtered and recrystallized from EtOAc to afford 1-{[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]methyl}-4-piperidinecarboxylic acid (E57) (140 mg). δH (DMSO-d6, 400 MHz): 1.37 (6H, d), 1.49-2.21 (7H, m), 2.84-2.87 (2H, m), 3.65 (5H, s), 4.86-4.93 (1H, m), 7.18 (1H, t), 7.31 (1H, s), 7.44 (1H, dd), 7.46 (1H, d), 7.91 (1H, dd), 8.14 (1H, dd), 8.21 (1H, d), 12.06 (1H, br s). MS (ES): C27H29ClN4O4 requires 508; found 380.1 (M—NC5H9COOH+).

후처리

  1. additioncharge
  2. concentrationThe reaction mixture was concentrated
  3. additionH2SO4 (0.1 M) solution was added dropwise until no further white precipitate
  4. customwas formed
  5. filtrationThe solid was filtered
  6. customrecrystallized from EtOAc

출처 및 근거

ORD 기록
ord-8bd5074371ed4ea49b8ed1a77171be18
출처 데이터셋
uspto-grants-2012_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08217028B2

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