Yield:-

Reaction Conditions:

Stage #1: methyl 6-methoxy-2-naphthylacetatewith n-butyllithium;diisopropylamine in tetrahydrofuran at -78 - -40;
Stage #2: iodomethane-d3 in tetrahydrofuran at -78 - -40;

Steps:

5.5

Methyl 2-(6-methoxynaphthalen-2-yl)-J_j-propanoate:; At about -20 ⁰C, 2.5M n-butyllithium in tetrahydrofuran was added to a solution of diisopropylamine (1.95 g, 19.3 mmol, 1.48 equiv.) in tetrahydrofuran (20 mL). The mixture was stirred at about 0 ⁰C for about 30 minutes. After cooling the mixture to about -78 ⁰C, a solution of methyl 2-(6-methoxynaphthalen-2-yl)acetate (3 g, 13 mmol, 1.00 equiv.) in tetrahydrofuran (30 mL) was then added. The mixture was stirred at about -40 ⁰C for about 40 minutes. The mixture was cooled to about -78 ⁰C, and then iodomethane (2.24 g, 15.4 mmol, 1.18 equiv.) was added. The mixture was stirred at about -40 ⁰C for about 1 hour, and then a saturated aqueous solution of ammonium chloride (50 mL) was added. Standard extractive workup with ethyl acetate (2 x 50 mL) gave the title product as a brown oil (3.2 g; (crude)). LC-MS: m/z = 248 (MH)⁺. ¹H NMR (300 MHz, CHCl₃) δ: 7.69-7.74 (m, 3H), 7.51 (dd, / = 8.4, 1.8 Hz, IH), 7.14-7.18 (m, 2H), 3.94 (s, 3H), 3.87 (s, IH), 3.69 (s, 3H).

References:

WO2010/129505,2010,A2 Location in patent:Page/Page column 37-38