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

HRID 718468ノート

反応式

HRID 718468 の反応式
[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[CH2:26][CH2:25][CH:24]([CH3:27])[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]([CH3:45])=[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[CH2:26][CH2:25][CH:24]([CH3:27])[CH2:23][CH2:22]1)[C:9]([OH:11])=[O:10])([CH3:6])([CH3:5])[CH3:4]

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2 回HCID 118307686(S)-isopropyl 2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethyl-4-(4-methylpiperidin-1-yl)pyridin-3-yl)acetate

生成物 1

HCID 118307846(S)-2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethyl-4-(4-methylpiperidin-1-yl)pyridin-3-yl)acetic acid収率 48%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

反応条件

温度
85 °C

実験手順

The 1.32 mL of 1M sodium hydroxide (52.8 mg, 1.32 mmol) was added to a (S)-isopropyl 2-(tert-butoxy)-2-(5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethyl-4-(4-methylpiperidin-1-yl)pyridin-3-yl)acetate (130 mg, 0.22 mmol) in ethanol (1 mL) and stirred for 24 h at 85° C. An additional 0.31 mL sodium hydroxide was added and the reaction was continued for 24 h. 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)-2,6-dimethyl-4-(4-methylpiperidin-1-yl)pyridin-3-yl)acetic acid 58 mg (48%) as a mixture of diastereomers. 1H NMR (500 MHz, DMSO-d6) δ 7.40-7.37 (m, 2H), 7.19 (d, J=9.2 Hz, 1H), 7.14 (t, J=8.8 Hz, 2H), 7.00-6.95 (m, 3H), 5.84 (s, 1H), 4.22 (t, J=6.6 Hz, 2H), 3.44-3.39 (m, 4H), 3.06 (t, J=6.6 Hz, 2H), 2.43 (s, 3H), 2.03 (s, 3H), 1.72-1.68 (m, 1H), 1.49 (d, J=12.1 Hz, 1H), 1.34 (d, J=7.0 Hz, 1H), 1.24-1.20 (m, 1H), 1.12 (s, 9H), 1.06-1.01 (m, 1H), 0.83 (d, J=3.7 Hz, 3H). UPLC (M+H)=549.6.

後処理

  1. waitthe reaction was continued for 24 h
  2. extractionextracted with EtOAc
  3. washthe organic layer was washed with brine
  4. dry with materialdried (MgSO4)
  5. customThe crude material was purified by prep HPLC

出典と根拠

ORDレコード
ord-4a7fde5b43124059bc4b700d7353924f
出典データセット
uspto-grants-2015_11
特許番号
US09193720B2

反応ノート

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