Water → 6-Methoxy-1-methyl-1-(trifluoromethyl)-3,4-dihydro-1H-2-benzopyran-3-ol

To a solution 6-methoxy-1-methyl-1-trifluoromethyl-isochroman-3-one (1.50 g, 5.76 mmol) in tetrahydrofuran (30 mL) at 0° C. was added sodium borohydride (0.240 g, 6.34 mmol) followed by boron trifluoride diethyl ether complex (0.992 g, 8.07 mmol). The reaction mixture was warmed to room temperature and was stirred overnight. The reaction mixture was added to water (75 mL) and extracted with methyl-tert-butyl ether (75 mL). The layers were separated and the organic layer was washed with 1N aqueous hydrochloric acid (50 mL), dried over magnesium sulfate, filtered, and concentrated to afford 6-methoxy-1-methyl-1-trifluoromethyl-isochroman-3-ol as an oil and a mixture of a and b anomers (1.19 g, 79%). Data reported for the major diastereoisomer. 1H NMR (400 MHz, CDCl3) δ1.74 (s, 3), 2.85 (dd, 1, J=15.7, 4.3), 2.88-2.99 (m, 1), 3.11 (dd, 1, J=15.7, 3.2), 3.80 (s, 3), 5.63 (t, 1, J=3.7), 6.69 (d, 1, J=2.7), 6.82 (dd, 1, J=8.7, 2.7), 7.22-7.27 (m, 1). 13C NMR (100 MHz, CDCl3, data reported for identifiable signals of the major diastereoisomer) δ24.52, 35.46, 55.16, 90.71, 113.11, 113.98, 125.22, 127.57, 132.98, 159.59. IR 3439, 2949,1735, 1613, 1506, 1166, 1141, 1070cm−1

1. extractionextracted with methyl-tert-butyl ether (75 mL)
2. customThe layers were separated
3. washthe organic layer was washed with 1N aqueous hydrochloric acid (50 mL)
4. dry with materialdried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated

ORD record

ord-acdad27a87004886af353de74e9d4460

Source dataset

uspto-grants-2002_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06486325B1