Sodium Hydroxide → [7-(5-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid

HRID 1514274노트

반응식

HRID 1514274 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:33]=[CH:32][C:20]4[CH2:21][CH2:22][N:23]([CH2:26][C:27]([O:29]CC)=[O:28])[CH2:24][CH2:25][C:19]=4[CH:18]=3)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[OH-].[Na+]>CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:33]=[CH:32][C:20]4[CH2:21][CH2:22][N:23]([CH2:26][C:27]([OH:29])=[O:28])[CH2:24][CH2:25][C:19]=4[CH:18]=3)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:10])[CH3:11]

참가 물질

4

반응물 2

HCID 14798Sodium HydroxideHCID 59403517Ethyl [7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetate

생성물 1

HCID 44128908[7-(5-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetic acid수율 29%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

A solution of ethyl [7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl]acetate (Preparation 46) (77 mg, 0.164 mmol) in methanol (30 ml) was stirred at room temp and sodium hydroxide (3 ml, 6.00 mmol) added. The reaction mixture was stirred at room temperature overnight. The solvent was removed in vacuo, the solid was triturated with methanol (˜5 ml) and the resultant solid filtered off and dried. The solid was suspended in methanol (˜30 ml) and acetic acid added to take the pH of the solution to 5-6, the solvent was removed in vacuo. The resultant residue was dissolved in DCM (˜30 ml) and water (˜30 ml) and the layers partitioned. The aqueous was re-extracted with DCM (˜20 ml) and the combined organics were passed through a phase separation cartridge and the solvent reduced in vacuo. The resultant residue was dried in a drying pistol at 60° C. to yield the title compound (22 mg, 0.047 mmol, 29% yield) as an off white solid. δH (d6DMSO, 400 MHz): 8.19 (1H, s), 8.11 (1H, d), 7.82-7.90 (2H, m), 7.44 (1H, d), 7.36 (1H, d), 4.89 (1H, sept), 3.34 (2H, s), 3.07-2.98 (4H, m), 2.91-2.86 (4H, m), 1.37 (6H, d. MS (ES+): C23H2435ClN3O4 requires 441; found 442 [M+H]+.

후처리

  1. customThe solvent was removed in vacuo
  2. customthe solid was triturated with methanol (˜5 ml)
  3. filtrationthe resultant solid filtered off
  4. customdried
  5. additionacetic acid added
  6. customthe solvent was removed in vacuo
  7. dissolutionThe resultant residue was dissolved in DCM (˜30 ml)
  8. customwater (˜30 ml) and the layers partitioned
  9. extractionThe aqueous was re-extracted with DCM (˜20 ml)
  10. customthe combined organics were passed through a phase separation cartridge
  11. dry with materialThe resultant residue was dried in a drying pistol at 60° C.

출처 및 근거

ORD 기록
ord-78bdfdb708534e298353b152647998a3
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08222245B2

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