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 63964노트

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HRID 63964 반응식
[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]

참가 물질

5

반응물 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

생성물 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 acid수율 38%

시약·촉매·용매 2

HCID 702Ethanol용매HCID 8028Tetrahydrofuran용매

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온도
60 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-051b9b765ec64b73b67942f5c7f2d19e
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09447116B2

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