Trimethyl borate → HCID 57972818, compound

In a flask equipped with a Soxhlet extractor containing 4 Å molecular sieves (pellets), (R)-binaphthol (716 mg) dissolved in dichloromethane (35 ml) was added. To the solution, was added trimethoxyborane (279 μl) and the mixture was heated to reflux under nitrogen atmosphere for 2 hours. The solution was concentrated under nitrogen atmosphere, and the resulting residue was dissolved in dichloromethane to give a dichloromethane solution of a chiral boron catalyst (8.0 ml). Vinyl-carbamic acid naphthalen-1-ylmethyl ester (227 mg) was dissolved in a mixture of toluene (2.5 ml) and dichloromethane (1.5 ml) and a 0.4M propylidene-(4-trifluoromethyl-phenyl)-amine/dichloromethane solution (2.75 ml) was added. Thereto was added the dichloromethane solution of a chiral boron catalyst prepared above (1.6 ml) dropwise under nitrogen atmosphere at 0° C. over 30 minutes. The mixture was stirred at the same temperature for 2 hours, then allowed to warm to room temperature, and the stirring was continued overnight. To the reaction mixture, was added a 0.5N NaOH aq. solution and extracted with ether. The organic layer was washed with a saturated brine twice, dried over magnesium sulfate and concentrated in vacuo. The resulting residue was purified by column chromatography (silica gel; hexane:ethyl acetate=19:1→7:3) to give the titled compound (331 mg). MS (m/z): 429 [M+H]+. Enantioselectivity was 96% ee determined by HPLC using CHIRALPAK IB (DAICEL CHEMICAL INDUSTRIES, LTD.), hexane:ethanol=9:1, flow rate=5 ml/min.

1. customIn a flask equipped with a Soxhlet extractor
2. additionwas added
3. temperaturethe mixture was heated
4. temperatureto reflux under nitrogen atmosphere for 2 hours
5. concentrationThe solution was concentrated under nitrogen atmosphere
6. dissolutionthe resulting residue was dissolved in dichloromethane
7. customto give a dichloromethane solution of a chiral boron catalyst (8.0 ml)
8. customprepared above (1.6 ml) dropwise under nitrogen atmosphere at 0° C. over 30 minutes
9. waitthe stirring was continued overnight
10. extractionextracted with ether
11. washThe organic layer was washed with a saturated brine twice
12. dry with materialdried over magnesium sulfate
13. concentrationconcentrated in vacuo
14. customThe resulting residue was purified by column chromatography (silica gel; hexane:ethyl acetate=19:1→7:3)

ORD record

ord-c6289d2138124978b4a9eae403ae7582

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08084611B2