Acetic Acid → (R)-2-(((S)-3,3-Dimethyl-2,3-dihydro-1H-inden-1-yl)amino)-2-phenylethanol

Temperatur

0 °C

To a solution of 3,3-dimethylindan-1-one (925 mg, 5.77 mmol) and (R)-(−)-2-phenylglycinol (893 mg, 6.51 mmol) in toluene (10.0 mL) was added p-toluenesulfonic acid monohydrate (62.5 mg, 0.328 mmol). The reaction was heated to reflux under an atmosphere of nitrogen for 90 min. At this point, the mixture was cooled and diluted with toluene (10.0 mL). The mixture was washed with saturated aqueous sodium bicarbonate solution and water. The organic layer was concentrated in vacuo and the residue was dissolved in THF (10.0 mL) and cooled to 0° C. Acetic acid (1.13 mL, 19.9 mmol) was added, followed by sodium borohydride (251 mg, 6.64 mmol) and the reaction was allowed to warm to rt overnight. The mixture was partitioned between DCM and saturated aqueous sodium bicarbonate solution. The organic layer was concentrated and silica gel chromatography eluting with a gradient of 5 to 35% EtOAc in DCM afforded the title compound (1.49 g, 74%). LC/MS: Rt=1.92 min, ES+ 282 (AA standard).

1. temperatureThe reaction was heated
2. temperatureto reflux under an atmosphere of nitrogen for 90 min
3. temperatureAt this point, the mixture was cooled
4. washThe mixture was washed with saturated aqueous sodium bicarbonate solution and water
5. concentrationThe organic layer was concentrated in vacuo
6. dissolutionthe residue was dissolved in THF (10.0 mL)
7. temperatureto warm to rt overnight
8. customThe mixture was partitioned between DCM and saturated aqueous sodium bicarbonate solution
9. concentrationThe organic layer was concentrated
10. washsilica gel chromatography eluting with a gradient of 5 to 35% EtOAc in DCM

ORD-Eintrag

ord-3d89567f7da2417cbe77edb6647d0cf3

Quelldatensatz

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08207177B2