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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
ノート
印刷プレビュー

反応式

HRID 718465 の反応式
[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]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

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

生成物 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 acid収率 47.4%

試薬・触媒・溶媒

1
HCID 702Ethanol溶媒

反応条件

温度
90 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-c5563ba1cc4049f1b729125d8d59d441
出典データセット
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09193720B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート