4-Fluoroaniline → (4aR,5R,8aS)-5-[(4-fluorophenyl)amino]octahydro-4-aH-isochromen-4a-ol

To a mixture of 4-fluoroaniline (0.119 g, 1.07 mmol) in CH2Cl2 (1 mL) at 0° C. was added trimethylaluminum (2M in toluene, 0.535 mL) dropwise. The mixture was warmed to rt and stirred for 30 min. A mixture of cis and trans octahydrooxireno[e]isochromene (0.033 g, 0.214 mmol) in CH2Cl2 (1 mL) was then added and the mixture was stirred at rt overnight. The reaction mixture was cooled to 0° C. and treated with 50% NaOH (1 mL) then water (1 mL). It was diluted with more water and extracted 3× with CH2Cl2. The combined organics were dried, filtered and concentrated. The residue was purified by column chromatography to give the title compound. 1H NMR (500 MHz, CDCl3) δ 6.92 (t, 2H, J=8.8 Hz), 6.71 (dd, 2H, J=4.2 Hz, 8.8 Hz), 3.81-3.87 (m, 1H), 3.61 (dd, 1H, J=4.6 Hz, 11.2 Hz), 3.50 (t, 1H, J=11.0 Hz), 3.32 (s, 1H), 2.15-2.26 (m, 1H), 1.89-2.07 (m, 2H), 1.59-1.69 (m, 2H), 1.45-1.58 (m, 1H), 1.20-1.37 (m, 4H). HRMS (ES) m/z M+H calc'd.: 266.1551. found: 266.1549

1. additionwas then added
2. stirringthe mixture was stirred at rt overnight
3. temperatureThe reaction mixture was cooled to 0° C.
4. extractionextracted 3× with CH2Cl2
5. customThe combined organics were dried
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue was purified by column chromatography

ORD record

ord-f267c5b6862a4c7d8241a8196ef2163a

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08829196B2