Acetovanillone → (R)-N-((R)-1-(4-hydroxy-3-methoxyphenyl)ethyl)-2-methylpropane-2-sulfinamide

To a THF (63 ml) solution of 1-(4-hydroxy-3-methoxyphenyl)ethanone (4.99 g, 30.0 mmol, purchased from TCI) and (R)-(+)-2-methyl-2-propanesulfinylamide (4.00 g, 33.0 mmol), titanium(IV) ethoxide (63.0 ml, 0.30 mol) was added under a nitrogen atmosphere and the mixture was refluxed with stirring for 20 hours. After imine formation was confirmed with LC-MS, the mixture was cooled to r.t. and the imine solution was added dropwise to a suspension of sodium borohydride (3.41 g, 90.1 mmol) in THF (50 mL) at 0° C. under nitrogene atmosphere. After stirring at room temperature for 3 hours, the reaction mixture was partitioned with water and ethanol, then the mixture was stirred for 1 hour at room temperature. The mixture was filtered through a Celite pad, and the filtrate was evaporated and concentrated in vacuo. The mixture was dissolved in EtOAc (500 ml), washed with 1N hydrochloric acid (300 ml), saturated aqueous sodium bicarbonate (300 ml), and brine (300 ml), and the organic layer was dried over sodium sulfate. Removal of the solvent gave a residue, which was chromatographed on a column of silica gel, eluting with EtOAc-hexane (1:1 to 3:1), to give the title compound (4.10 g, 50%) as a colorless syrup. 1H NMR (270 MHz, CDCl3) δ ppm 1.23 (9H, s), 1.49 (3H, d, J=6.6 Hz), 3.36 (1H, m), 3.89 (3H, s), 4.40-4.60 (1H, m), 5.71 (1H, s), 6.87 (3H, m).

1. temperaturethe mixture was refluxed
2. stirringAfter stirring at room temperature for 3 hours
3. customthe reaction mixture was partitioned with water and ethanol
4. stirringthe mixture was stirred for 1 hour at room temperature
5. filtrationThe mixture was filtered through a Celite pad
6. customthe filtrate was evaporated
7. concentrationconcentrated in vacuo
8. dissolutionThe mixture was dissolved in EtOAc (500 ml)
9. washwashed with 1N hydrochloric acid (300 ml), saturated aqueous sodium bicarbonate (300 ml), and brine (300 ml)
10. dry with materialthe organic layer was dried over sodium sulfate
11. customRemoval of the solvent
12. customgave a residue, which
13. customwas chromatographed on a column of silica gel
14. washeluting with EtOAc-hexane (1:1 to 3:1)

ORD record

ord-29e5a0f617f44aed8ec34de54959f51b

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08158650B2