1-Chloro-2-iodoethane → (S)-4-(2-chloro-9-ethyl-8-iodo-9H-purin-6-yl)-3-methylmorpholine

Participants

Reaction Conditions

Reaction Steps

To (S)-4-(2-chloro-9-ethyl-9H-purin-6-yl)-3-methylmorpholine (465.0 mg, 1.65 mmol) in anhydrous THF (6.7 mL) at −78° C. under N2 was added freshly prepared lithium diisopropylamide in THF (2.0 eq). The reaction was stirred at −78° C. under N2 for 2 hours, and 1-chloro-2-iodoethane (1.01 g, 5.78 mmol, 3.5 eq.) was added. The reaction mixture was then stirred at RT for 3 days and then quenched with saturated aqueous sodium ammonium chloride solution at 0° C. Volatile solvent was then evaporated in vacuo, and the crude was diluted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate, water and brine, then dried (Na2SO4), filtered and evaporated in vacuo. The resultant residue was purified by column chromotagraphy (Si-PPC, gradient 0 to 100% ethyl acetate in hexane) to give the desired compound as a foam (610.0 mg, 90.7%). 1H NMR (CDCl3, 400 MHz) δ ppm 5.28 (broad s, 2H), 4.17 (q, J=7.4 Hz, 2H), 4.00 (dd, J=11.3, 3.4 Hz, 1H), 3.75 (m, 2H), 3.59 (m, 1H), 3.48 (broad s, 1H), 1.37 (m, 6H); LC-MS m/z (method B2)=408 [M+H]+, RT=2.06 min.

Provenance & Evidence