Ammonia → HCID 68838179, compound

Temperature

-78 °C

To a solution of methyl 2-methoxy-naphthoate (1.00 g, 4.6 mmol) and tert-butyl alcohol (0.43 mL, 4.6 mmol) in anhydrous tetrahydrofuran (10 mL) at −78° C. under N2 was added anhydrous ammonia (˜20 mL), followed by the portionwise addition of potassium metal until a dark blue solution was maintained for >15 min. To the resulting mixture was added neohexyl iodide (0.5 g, 2.36 mmol), the mixture was stirred at −78° C. for 20 min, and then allowed to slowly warm to rt while evaporating the ammonia with a dry N2 stream. To the resulting suspension was added anhydrous tetrahydrofuran (10 mL), and the mixture was heated at 50° C. under N2 for 16 h. The reaction mixture was partitioned between saturated aq. NaHCO3 (20 mL) and ethyl acetate (3×20 mL), and the combined organic layers were dried over Na2SO4. The crude product was purified by column chromatography on silica gel using 19:1 hexanes:ethyl acetate to provide the title compound as a colorless gum (0.32 g, 23%). 1H NMR (300 MHz, CDCl3) δ ppm 7.11-7.23 (m, 4H), 5.06 (t, J=3.9 Hz, 1H), 3.61 (s, 3H), 3.60 (s, 3H), 3.54-3.57 (m, 2H), 2.20-2.31 (m, 1H), 2.00-2.11 (m, 1H), 0.82-0.94 (m, 1H), 0.75 (s, 9H), 0.45-0.57 (m, 1H).

1. temperaturewas maintained for >15 min
2. temperatureto slowly warm to rt
3. customwhile evaporating the ammonia with a dry N2
4. additionTo the resulting suspension was added anhydrous tetrahydrofuran (10 mL)
5. temperaturethe mixture was heated at 50° C. under N2 for 16 h
6. customThe reaction mixture was partitioned between saturated aq. NaHCO3 (20 mL) and ethyl acetate (3×20 mL)
7. dry with materialthe combined organic layers were dried over Na2SO4
8. customThe crude product was purified by column chromatography on silica gel using 19:1 hexanes

ORD record

ord-b6ee59f6920948e7a503bce5a93579e4

Source dataset

uspto-grants-2009_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07517876B2