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

HRID 718472
ノート
印刷プレビュー

反応式

HRID 718472 の反応式
[OH-].[K+].[CH2:3]([CH:10]1[CH2:15][CH2:14][N:13]([C:16]2[C:21]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][C:31]4[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=4)=[CH:24][CH:23]=3)=[C:20]([CH3:38])[N:19]=[C:18]([CH3:39])[C:17]=2[C@H:40]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])[C:41]([O:43]C(C)C)=[O:42])[CH2:12][CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl>C(O)C>[CH2:3]([CH:10]1[CH2:11][CH2:12][N:13]([C:16]2[C:21]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH2:29][CH2:30][C:31]4[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=4)=[CH:24][CH:23]=3)=[C:20]([CH3:38])[N:19]=[C:18]([CH3:39])[C:17]=2[C@H:40]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])[C:41]([OH:43])=[O:42])[CH2:14][CH2:15]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
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 118307842(S)-isopropyl 2-(4-(4-benzylpiperidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate

生成物 1

HCID 118307696(S)-2-(4-(4-benzylpiperidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetic acid収率 25.3%

試薬・触媒・溶媒 1

HCID 702
Ethanol
溶媒

反応条件

温度
90 °C

実験手順

The potassium hydroxide (86 mg, 1.54 mmol) was added to a station (S)-isopropyl 2-(4-(4-benzylpiperidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate (102 mg, 0.154 mmol) in ethanol (3 mL) and stirred for 12 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 give (S)-2-(4-(4-benzylpiperidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetic acid 24.3 mg (25%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 7.40-7.37 (m, 2H), 7.24-7.22 (m, 2H), 7.18-7.12 (m, 4H), 7.10 (t, J=7.7 Hz, 2H), 6.99-6.92 (m, 3H), 5.77 (s, 1H), 4.21 (t, J=6.6 Hz, 2H), 3.47-3.37 (m, 4H), 3.06 (t, J=6.2 Hz, 2H), 2.46-2.44 (m, 2H), 2.42 (s, 3H), 2.01 (s, 3H), 1.66 (t, J=10.6 Hz, 1H), 1.44-1.41 (m, 1H), 1.34-1.22 (m, 3H), 1.09 (m, 9H). UPLC (M+H)=625.4.

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-c40fcb6c5fcd47b3a09c795f0623429f
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…

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