N-(2-methylpropylidene)hydroxylamine

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirring solution of 1.0 g (11.5 mmol) of isobutyraldehyde oxime, 0.9 g (12.1 mmol) of propargyl chloride, and 0.7 mL (5.02 mmol) of Et3N in 30 mL of CH2Cl2 at 0° C. was added 125 mL of sodium chlorite solution (>4% chlorine). The ice bath was removed and stirring was continued with warming to r.t. After 1.5 h, CH2Cl2 was added, and the organic layer was washed with 20 mL of brine, dried over Na2SO4, filtered, and concentrated. Purification by flash silica gel chromatography (10% EtOAc/hexanes) provided 1.14 g of 5-(chloromethyl)-3-isopropylisoxazole as a pale yellow liquid in about 62% yield. (60%) The ice bath was removed CH2Cl2 was added the organic layer was washed with 20 mL of brine dried over Na2SO4 filtered concentrated Purification by flash silica gel chromatography (10% EtOAc/hexanes)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-methylpropionaldehyde oxime (0.047 g, 0.54 mmol) in anhydrous THF (3 mL) was added a solution of potassium tert-butoxide (KOtBu, 1 M in THF; 0.50 mL, 0.50 mmol) at room temperature, and the resulting pale-yellow mixture was stirred for 15 min. To the resulting solution was added 2-fluorobenzyl-(5-fluoro-2-methanesulfonylpyrimidin-4-yl)amine (0.125 g, 0.42 mmol), and the resulting tan mixture was stirred at room temperature for 16 h. The entire reaction mixture was adsorbed to Celite (2.5 g) and the adsorbed material was purified by flash chromatography (40 g SiO2; 0→100% EtOAc/hexanes) to give 2-methylpropionaldehyde O-[5-fluoro-4-(2-fluorobenzylamino)-pyrimidin-2-yl]oxime (0.71 g, 56%) as a colorless oil: IR (thin film) 3261, 3179, 3049, 2973, 2936, 2872, 1676, 1622, 1568, 1531, 1491, 1457, 1409, 1372 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.91 (d, J=2.5 Hz, 1H), 7.71 (d, J=7.5 Hz, 1H), 7.43 (t, J=6.9 Hz, 1H), 7.29 (m, J=7.6 Hz, 1H), 7.09 (m, 2H), 5.42 (s, 1H), 4.76 (d, J=5.8 Hz, 2H), 2.79 (dq, J=13.9, 6.9 Hz, 1H), 1.18 (d, J=6.8 Hz, 6H); ESIMS m/z 307 ([M+H]+), 305 ([M−H]−). the resulting tan mixture was stirred at room temperature for 16 h The entire reaction mixture the adsorbed material was purified by flash chromatography (40 g SiO2; 0→100% EtOAc/hexanes)