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Phenol → (R)-tert-butyl (3-(3-((1-acetylpiperidin-4-yl)methoxy)phenyl)-3-hydroxypropyl)carbamate

HRID 2277051
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HRID 2277051 반응식
C1(O)C=CC=CC=1.[OH:8][C@@H:9]([C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([OH:26])[CH:21]=1)[CH2:10][CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16].C([O-])([O-])=O.[K+].[K+].CC1C=CC(S(O[CH2:44][CH:45]2[CH2:50][CH2:49][N:48]([C:51](=[O:53])[CH3:52])[CH2:47][CH2:46]2)(=O)=O)=CC=1>CN(C=O)C.CCOC(C)=O>[C:51]([N:48]1[CH2:49][CH2:50][CH:45]([CH2:44][O:26][C:22]2[CH:21]=[C:20]([C@H:9]([OH:8])[CH2:10][CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH:25]=[CH:24][CH:23]=2)[CH2:46][CH2:47]1)(=[O:53])[CH3:52]
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참가 물질

7

반응물 4

HCID 996PhenolHCID 11430Potassium CarbonateHCID 66569167(1-Acetylpiperidin-4-yl)methyl 4-methylbenzenesulfonateHCID 90405310(R)-tert-butyl 3-hydroxy-3-(3-hydroxyphenyl)propylcarbamate

생성물 1

HCID 131733438(R)-tert-butyl (3-(3-((1-acetylpiperidin-4-yl)methoxy)phenyl)-3-hydroxypropyl)carbamate

시약·촉매·용매 2

HCID 6228
Dimethylformamide
용매
HCID 8857Ethyl Acetate용매

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온도
90 °C

실험 절차

Phenol (7, Intermediate I) (0.850 g, 3.20 mmol) and K2CO3 (1.32 g, 9.60 mmol) were added to a solution of (1-acetylpiperidin-4-yl)methyl 4-methylbenzenesulfonate (1.0 g, 3.20 mmol) in DMF (10 mL). The reaction mixture was heated at 90° C. overnight. The reaction mixture was diluted with EtOAc and washed with water and brine. Organic layer was dried over anhydrous Na2SO4) and concentrated under reduced pressure to give after purification by column chromatography to give (R)-tert-butyl (3-(3-((1-acetylpiperidin-4-yl)methoxy)phenyl)-3-hydroxypropyl)carbamate as a colorless semi solid. Yield (600 mg, 46%); 1H NMR (400 MHz, DMSO-d6); δ 7.18 (d, J=4.0 Hz, 1H), 6.93 (s, 1H), 6.86 (d, J=7.6 Hz, 1H), 6.76 (d, J=6.0 Hz, 1H), 5.17 (d, J=4.4 Hz, 1H), 4.50 (d, J=4.8 Hz, 1H), 4.39 (d, J=11.6 Hz, 1H), 3.81 (d, J=6.4 Hz, 2H), 3.06-2.94 (m, 4H), 1.99 (s, 3H), 1.78 (t, J=14 Hz, 2H), 1.65 (t, J=7.2, 2H), 1.36 (s, 9H), 1.23 (s, 3H), 1.55-0.88 (m, 1H); MS: m/z 407.05 [M+H]+.

후처리

  1. washwashed with water and brine
  2. dry with materialOrganic layer was dried over anhydrous Na2SO4) and
  3. concentrationconcentrated under reduced pressure
  4. customto give
  5. customafter purification by column chromatography

출처 및 근거

ORD 기록
ord-c682c92df6a94351acaf235bd83eaeb9
출처 데이터셋
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09133154B2

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