Hydrochloric Acid → 5-Fluoro-2-(thiophen-2-ylmethoxy)pyrimidin-4-ylamine

Participants

Reaction Conditions

Reaction Steps

To a mixture of 4-amino-2-chloro-5-fluoropyrimidine (2.00 g, 13.5 mmol) and thiophen-2-ylmethanol (1.92 g, 16.9 mmol) with a magnetic stir bar in a 20 mL Biotage Initiator microwave reaction vessel was added t-BuOK (17.0 mL of 1M in t-BuOH, 17.0 mmol). The resulting mixture was sealed with a Biotage Initiator microwave septa cap and heated in a Biotage Initiator microwave to 100° C. for 30 min. The heating cycle was repeated (2×) for a total reaction time of 90 min. The contents were poured into ice-water and the pH was adjusted to neutral with 2N HCl. The resulting solid was filtered and washed with water (2×) and then 20% ether/hexanes (100 mL). The remaining solid was dried overnight at 50° C. under vacuum to give 4.17 g (68%) of 5-fluoro-2-(thiophen-2-ylmethoxy)pyrimidin-4-ylamine as a pale yellow powder: mp 92-94° C.; 1H NMR (300 MHz, CDCl3) δ 7.92 (d, J=2.7 Hz, 1H), 7.29 (m, 1H), 7.13 (d, J=3.6 Hz, 1H), 6.97 (m, 1H), 5.46 (s, 2H), 5.17 (br s, 2H); MS (ESI) m/z 226 (M+H)+.

Provenance & Evidence