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

HRID 2277051
ノート
印刷プレビュー

反応式

HRID 2277051 の反応式
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]
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

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228
Dimethylformamide
溶媒
HCID 8857Ethyl Acetate溶媒

反応条件

温度
90 °C

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-c682c92df6a94351acaf235bd83eaeb9
出典データセット
uspto-grants-2015_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09133154B2

反応ノート

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