Pyrimidine, 2-ethynyl-4-methoxy- (9CI) synthesis

Yield: 85%

Reaction Conditions:

Stage #1:4-Methoxy-2-<(trimethylsilyl)ethynyl>pyrimidine with tetrabutyl ammonium fluoride;acetic acid in tetrahydrofuran at 20; for 0.0833333 h;
Stage #2: with potassium carbonate in tetrahydrofuran;water

Steps:

1.b
Tetrabutylammonium fluoride (0.97 mL of a 1M solution in tetrahydrofuran, 0.97 mmol) was added to a stirred solution of 4-methoxy-2-[(trimethylsilyl)ethynyl]pyrimidine (Preparation 1a, 0.20 g, 0.97 mmol) in tetrahydrofuran (1.4 mL) and acetic acid (56 μ) at room temperature. After 5 minutes, 10% aqueous potassium carbonate solution was added to the reaction mixture and the mixture was extracted with dichloromethane. The organic layer was separated, dried (MgS0₄) and evaporated. Purification of the residue by flash chromatography (dichloromethane) gave the title compound (0.11 g, 85%) as a pale orange solid.LRMS (m/z): 135 (M+1)⁺.¹H-NMR δ (300 MHz, CDCI₃): 3.1 (s, 1H), 4.0 (s, 3H), 6.7 (d, 1 H), 8.4 (d, 1 H).

References:

ALMIRALL, S.A.;BACH TAŇA, Jordi;PAGES SANTACANA, Lluis, Miquel;TALTAVULL MOLL, Joan;EASTWOOD, Paul, Robert;GONZALEZ RODRIGUES, Jacob;GIULIO MATASSA, Victor WO2011/101161, 2011, A1 Location in patent:Page/Page column 82