Hydrochloric Acid → (2R)-3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]-2-methylpropanoic acid

HRID 1512895노트

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HRID 1512895 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][C@@H:28]([CH3:33])[C:29]([O:31]C)=[O:30])[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[OH-].[Na+].Cl>C1COCC1>[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][C@@H:28]([CH3:33])[C:29]([OH:31])=[O:30])[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:10])[CH3:11]

참가 물질

5

반응물 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 59146133methyl (2R)-3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]-2-methylpropanoate

생성물 1

HCID 44548063(2R)-3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]-2-methylpropanoic acid수율 64.4%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
50 °C

실험 절차

To a solution of methyl (2R)-3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]-2-methylpropanoate (D60) (80 mg) in THF (5 mL) was added aqueous NaOH (2 M, 1 mL). The reaction was stirred at 50° C. for 16 h. The mixture was acidified with aqueous HCl (2 M) to pH 4-5, partitioned between ethyl acetate (50 mL) and water (50 mL). The organic phase was washed with water (25 mL) and brine (25 mL), dried over anhydrous sodium sulphate and evaporated to give the crude product, which was purified by Mass Directed Auto Prep to afford (2R)-3-[7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indol-3-yl]-2-methylpropanoic acid (E36) (50 mg). δH (DMSO-d6, 400 MHz): 1.11 (3H, d), 1.35 (6H, d), 2.75 (2H, m), 3.04 (1H, m), 3.62 (3H, s), 4.88 (1H, m), 7.17 (2H, m), 7.43 (2H, m), 7.79 (1H, d), 8.13 (1H, dd), 8.20 (1H, d), 12.13 (1H, br s). MS (ES): C24H24ClN3O4 requires 453; found 454.2 (M+H+).

후처리

  1. custompartitioned between ethyl acetate (50 mL) and water (50 mL)
  2. washThe organic phase was washed with water (25 mL) and brine (25 mL)
  3. dry with materialdried over anhydrous sodium sulphate
  4. customevaporated
  5. customto give the crude product, which
  6. customwas purified by Mass Directed Auto Prep

출처 및 근거

ORD 기록
ord-e467a8c724084e449f1f3ead3f5b7fa0
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08217028B2

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