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Hydrochloric Acid → (S)-2-(tert-butoxy)-2-(5-(4-(4-fluoro-phenethoxy)phenyl)-4-(3-isopropylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)acetic acid

HRID 718463
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HRID 718463 반응식
[OH-].[Na+].[C:3]([O:7][C@@H:8]([C:15]1[C:16]([CH3:45])=[N:17][C:18]([CH3:44])=[C:19]([C:28]2[CH:33]=[CH:32][C:31]([O:34][CH2:35][CH2:36][C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=3)=[CH:30][CH:29]=2)[C:20]=1[N:21]1[CH2:24][CH:23]([CH:25]([CH3:27])[CH3:26])[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]([CH3:45])=[N:17][C:18]([CH3:44])=[C:19]([C:28]2[CH:29]=[CH:30][C:31]([O:34][CH2:35][CH2:36][C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=3)=[CH:32][CH:33]=2)[C:20]=1[N:21]1[CH2:24][CH:23]([CH:25]([CH3:27])[CH3:26])[CH2:22]1)[C:9]([OH:11])=[O:10])([CH3:6])([CH3:4])[CH3:5]
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HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 118307787(S)-isopropyl 2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-4-(3-isopropylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)acetate

생성물 1

HCID 118307677(S)-2-(tert-butoxy)-2-(5-(4-(4-fluoro-phenethoxy)phenyl)-4-(3-isopropylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)acetic acid수율 74%

시약·촉매·용매 1

HCID 702
Ethanol
용매

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온도
90 °C

실험 절차

The 0.98 mL of 1M sodium hydroxide (39.3 mg, 0.98 mmol) was added to a solution (S)-isopropyl 2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-4-(3-isopropylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)acetate (145 mg, 0.245 mmol) in ethanol (3 mL) and stirred for 18 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-fluoro-phenethoxy)phenyl)-4-(3-isopropylazetidin-1-yl)-2,6-dimethylpyridin-3-yl)acetic acid 99.4 mg (74%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 7.36 (t, J=8.1 Hz, 2H), 7.30 (br. s, 1H), 7.12 (t, J=8.8 Hz, 2H), 7.1 (d, J=8.1 Hz, 1H), 6.97 (d, J=8.1 Hz, 1H), 6.86 (br. s, 1H), 4.93 (s, 1H), 4.21 (t, J=6.6 Hz, 2H) 3.96 (br. s, 1H), 3.86 (br. s, 1H), 3.70 (br. s, 1H), 3.47 (br. s, 1H), 3.03 (t, J=6.2 Hz, 2H), 2.39 (s, 3H), 2.07 (s, 3H), 2.05-2.01 (m, 1H), 1.52-1.47 (m, 1H), 1.08 (s, 9H), 0.65 (d, J=6.2 Hz, 6H). UPLC (M+H)=549.5.

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-2006ae40cfc64a4d927e4a9492f87834
출처 데이터셋
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09193720B2

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