Phenol → tert-butyl ((3R)-3-hydroxy-3-(3-((tetrahydro-2H-thiopyran-3-yl)methoxy)phenyl)propyl)carbamate

HRID 2277046ノート

反応式

HRID 2277046 の反応式
C([O-])([O-])=O.[K+].[K+].C1(O)C=CC=CC=1.[OH:14][C@@H:15]([C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([OH:32])[CH:27]=1)[CH2:16][CH2:17][NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22].CC1C=CC(S(O[CH2:44][CH:45]2[CH2:50][CH2:49][CH2:48][S:47][CH2:46]2)(=O)=O)=CC=1>CN(C=O)C>[OH:14][C@@H:15]([C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH2:44][CH:45]2[CH2:50][CH2:49][CH2:48][S:47][CH2:46]2)[CH:27]=1)[CH2:16][CH2:17][NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22]

参加物

6

反応物 4

HCID 996PhenolHCID 11430Potassium CarbonateHCID 90405310(R)-tert-butyl 3-hydroxy-3-(3-hydroxyphenyl)propylcarbamateHCID 90405933(tetrahydro-2H-thiopyran-3-yl)methyl 4-methylbenzenesulfonate

生成物 1

HCID 131733435tert-butyl ((3R)-3-hydroxy-3-(3-((tetrahydro-2H-thiopyran-3-yl)methoxy)phenyl)propyl)carbamate

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
100 °C

実験手順

K2CO3 (0.72 g, 5.24 mmol) and phenol (7, Intermediate I) (0.3 g, 1.05 mmol) were added to a solution of (tetrahydro-2H-thiopyran-3-yl)methyl 4-methylbenzenesulfonate (0.29 g, 1.10 mmol) in DMF (10 mL). The reaction mixture was heated at 100° C. under reflux overnight and then cooled. The reaction mixture was extracted with EtOAc, organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. Purification by flash chromatography (EtOAc:hexane 10-40% gradient) gave tert-butyl ((3R)-3-hydroxy-3-(3-((tetrahydro-2H-thiopyran-3-yl)methoxy)phenyl)propyl)carbamate as a light green solid. Yield (0.21 g, 52%); 1H NMR (400 MHz, CDCl3): δ 7.24 (t, J=8.0 Hz, 1H), 6.91 (d, J=8.0 Hz, 2H), 6.78 (d, 1H), 4.87 (bs, 1H), 4.71 (bs, 1H), 3.84-3.80 (m, 2H), 3.49 (bs, 1H), 3.21-3.13 (m, 2H), 2.82-2.77 (m, 1H), 2.62-2.47 (m, 3H), 2.18 (bs, 1H), 2.08-2.04 (m, 1H), 1.91-1.74 (m, 4H), 1.45 (s, 9H), 1.30-1.20 (m, 3H); MS: m/z 382.2 [M+H]+.

後処理

  1. temperatureunder reflux overnight
  2. temperaturecooled
  3. extractionThe reaction mixture was extracted with EtOAc, organic layer
  4. dry with materialwas dried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customPurification by flash chromatography (EtOAc:hexane 10-40% gradient)

出典と根拠

ORDレコード
ord-de8322f951dc4b978f5f94b347e43e3f
出典データセット
uspto-grants-2015_09
特許番号
US09133154B2

反応ノート

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