Sodium Hydroxide → Tert-butoxy[4-(2-hydroxy-4-methylphenyl)-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetic acid

HRID 63964ノート

反応式

HRID 63964 の反応式
[C:1]([O:5][CH:6]([C:12]1[C:13]([C:26]2[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][C:27]=2[OH:33])=[C:14]2[C:21]3[CH2:22][CH2:23][CH2:24][CH2:25][C:20]=3[S:19][C:15]2=[N:16][C:17]=1[CH3:18])[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>C(O)C.O1CCCC1>[C:1]([O:5][CH:6]([C:12]1[C:13]([C:26]2[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][C:27]=2[OH:33])=[C:14]2[C:21]3[CH2:22][CH2:23][CH2:24][CH2:25][C:20]=3[S:19][C:15]2=[N:16][C:17]=1[CH3:18])[C:7]([OH:9])=[O:8])([CH3:4])([CH3:3])[CH3:2]

参加物

5

反応物 2

HCID 14798Sodium HydroxideHCID 136372356Ethyl tert-butoxy[4-(2-hydroxy-4-methylphenyl)-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetate

生成物 1

HCID 136372357Tert-butoxy[4-(2-hydroxy-4-methylphenyl)-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetic acid収率 38%

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
60 °C

実験手順

To a stirred solution of the major diastereoisomeric pair of ethyl tert-butoxy[4-(2-hydroxy-4-methylphenyl)-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetate (Step 9, 214 mg, 458 μmol) in ethanol (5 mL) and tetrahydrofuran (5 mL) was added a solution of sodium hydroxide (2 N, aqueous, 2 mL, 2.75 mmol) and the reaction was stirred at 60° C. for 18 hours. The reaction was concentrated in vacuo until all organic solvents had been removed, the aqueous residue was then acidified with hydrochloric acid (2 N, aqueous) to pH 2. The precipitated solid was collected by filtration and washed with tert-butyl methyl ether (10 mL) and dried in vacuo to give a mixture of diastereoisomers of the title compound as a white solid, 76 mg, in a 38% yield. LC-MS (12 min acidic) 5.51 mins 81% pure by UV, ES+/APCI+ 440, ES−/APCI− 438. 1H NMR (400 MHz, CDCl3) δ ppm 1.04 (s, 9 H) 1.66-1.88 (m, 4 H) 2.09-2.21 (m, 2 H) 2.40 (s, 3 H) 2.73 (s, 3 H) 2.82 (t, 2 H) 5.33 (s, 1 H) 6.78 (s, 1 H) 6.85 (d, 1 H) 7.36 (d, 1 H).

後処理

  1. concentrationThe reaction was concentrated in vacuo until all organic solvents
  2. customhad been removed
  3. filtrationThe precipitated solid was collected by filtration
  4. washwashed with tert-butyl methyl ether (10 mL)
  5. customdried in vacuo
  6. customto give

出典と根拠

ORDレコード
ord-051b9b765ec64b73b67942f5c7f2d19e
出典データセット
uspto-grants-2016_09
特許番号
US09447116B2

反応ノート

読み込み中…