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

HRID 882469Notes

Reaction equation

HRID 882469 reaction equation
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

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-433700a7f3bf4139908538a26c404a92
Source dataset
uspto-grants-2015_03
Patent number
US08993807B2

Reaction notes

Loading…