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Hydrochloric Acid → (S)-2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-4-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetic acid

HRID 718465
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HRID 718465 반응식
[OH-].[K+].[C:3]([O:7][C@@H:8]([C:15]1[C:16]([CH3:52])=[N:17][C:18]([CH3:51])=[C:19]([C:35]2[CH:40]=[CH:39][C:38]([O:41][CH2:42][CH2:43][C:44]3[CH:49]=[CH:48][C:47]([F:50])=[CH:46][CH:45]=3)=[CH:37][CH:36]=2)[C:20]=1[N:21]1[CH2:26][CH2:25][CH:24]([C:27]2[O:31][N:30]=[C:29]([CH:32]([CH3:34])[CH3:33])[N:28]=2)[CH2:23][CH2:22]1)[C:9]([O:11]C(C)C)=[O:10])([CH3:6])([CH3:5])[CH3:4].Cl>C(O)C>[C:3]([O:7][C@@H:8]([C:15]1[C:16]([CH3:52])=[N:17][C:18]([CH3:51])=[C:19]([C:35]2[CH:36]=[CH:37][C:38]([O:41][CH2:42][CH2:43][C:44]3[CH:45]=[CH:46][C:47]([F:50])=[CH:48][CH:49]=3)=[CH:39][CH:40]=2)[C:20]=1[N:21]1[CH2:26][CH2:25][CH:24]([C:27]2[O:31][N:30]=[C:29]([CH:32]([CH3:33])[CH3:34])[N:28]=2)[CH2:23][CH2:22]1)[C:9]([OH:11])=[O:10])([CH3:6])([CH3:4])[CH3:5]
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참가 물질

5

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HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 118307752(S)-isopropyl 2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-4-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetate

생성물 1

HCID 118307745(S)-2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-4-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetic acid수율 47.4%

시약·촉매·용매 1

HCID 702Ethanol용매

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온도
90 °C

실험 절차

The potassium hydroxide (20.4 mg, 0.36 mmol) was added to a solution (S)-isopropyl 2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-4-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetate (25 mg, 0.036 mmol) in ethanol (1 mL) and stirred for 3 h at 90° C. The reaction mixture was neutralized with 1N HCl solution, extracted with EtOAc, and the organic layer was washed with brine, and dried (MgSO4). The crude material was purified by prep HPLC to afford (S)-2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-4-(4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetic acid 11 mg (47%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 7.41-7.39 (m, 2H), 7.23-7.22 (m, 1H), 7.17-7.13 (m, 2H), 7.02-7.01 (m, 2H), 6.96-6.94/6.86-6.84/6.80-6.77 (series m, 1H), 5.73 (br. s, 1H), 4.24 (t, J=6.6 Hz, 2H), 3.67-3.65 (m, 1H), 3.07 (t, J=6.6 Hz, 2H), 3.03-2.97 (m, 1H), 2.72-2.67 (m, 2H), 2.58-2.56 (m, 1H), 2.46 (s, 3H), 2.04 (s, 3H), 1.87-1.75 (m, 4H), 1.67-1.62 (m, 1H), 1.23 (d, J=6.6 Hz, 6H), 1.12 (s, 9H). UPLC (M+H)=645.4.

후처리

  1. extractionextracted with EtOAc
  2. washthe organic layer was washed with brine
  3. dry with materialdried (MgSO4)
  4. customThe crude material was purified by prep HPLC

출처 및 근거

ORD 기록
ord-c5563ba1cc4049f1b729125d8d59d441
출처 데이터셋
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09193720B2

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