Cesium carbonate → 2-(3-(3-(((1R,2S)-2-hydroxycyclohexyl)methoxy)phenyl)propyl)isoindoline-1,3-dione

HRID 1014647ノート

反応式

HRID 1014647 の反応式
CC1C=CC(S([O:11][CH2:12][C@H:13]2[CH2:18][CH2:17][CH2:16][CH2:15][C@@H:14]2[OH:19])(=O)=O)=CC=1.O[C:21]1[CH:22]=[C:23]([CH2:27][CH2:28][CH2:29][N:30]2[C:38](=[O:39])[C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[C:31]2=[O:40])[CH:24]=[CH:25][CH:26]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[OH:19][C@H:14]1[CH2:15][CH2:16][CH2:17][CH2:18][C@@H:13]1[CH2:12][O:11][C:25]1[CH:24]=[C:23]([CH2:27][CH2:28][CH2:29][N:30]2[C:31](=[O:40])[C:32]3[C:37](=[CH:36][CH:35]=[CH:34][CH:33]=3)[C:38]2=[O:39])[CH:22]=[CH:21][CH:26]=1

参加物

5

反応物 3

HCID 10796Cesium carbonateHCID 14970968((1R,2S)-2-hydroxycyclohexyl)methyl 4-methylbenzenesulfonateHCID 580275422-[3-(3-Hydroxyphenyl)propyl]isoindole-1,3-dione

生成物 1

HCID 673164482-(3-(3-(((1R,2S)-2-hydroxycyclohexyl)methoxy)phenyl)propyl)isoindoline-1,3-dione

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

A mixture of ((1R,2S)-2-hydroxycyclohexyl)methyl 4-methylbenzenesulfonate (0.334 g, 1.24 mmol), compound 58 (0.432 g, 1.54 mmol), cesium carbonate (0.562 g, 1.73 mmol) in anhydrous DMF (8 mL) was stirred at 60° C. under argon for 18 hrs, and then concentrated under reduced pressure. Water was added and the product was extracted with EtOAc three times. Combined fractions were washed with sat. NH4Cl, brine, and concentrated under reduced pressure. The residue was purified by flash chromatography (20% to 70% EtOAc/hexanes gradient) to afford 2-(3-(3-(((1R,2S)-2-hydroxycyclohexyl)methoxy)phenyl)propyl)isoindoline-1,3-dione as a colorless oil. Yield (0.191 g, 41%). 1H NMR (400 MHz, DMSO-d6) δ 7.76-7.85 (m, 4H), 7.09 (t, 7.6 Hz, 1H), 6.69-6.74 (m, 2H), 6.61-6.65 (m, 1H), 4.34 (d, J=4.1 Hz, 1H), 3.91 (dd, J=7.0, 9.2 Hz, 1H), 3.86-3.89 (m, 1H), 3.67 (dd, J=6.9, 9.2 Hz, 1H), 3.53-3.60 (m, 2H), 2.50 (t, J=7.6 Hz, 2H), 1.80-1.91 (m, 2H), 1.73-1.80 (m, 1H), 1.51-1.66 (m, 3H), 1.28-1.44 (m, 4H), 1.17-1.25 (m, 1H).

後処理

  1. concentrationconcentrated under reduced pressure
  2. additionWater was added
  3. extractionthe product was extracted with EtOAc three times
  4. washCombined fractions were washed with sat. NH4Cl, brine
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography (20% to 70% EtOAc/hexanes gradient)

出典と根拠

ORDレコード
ord-ce85fac0295f412c8c3ba9ece41f9f3c
出典データセット
uspto-grants-2011_07
特許番号
US07982071B2

反応ノート

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