1-[(5-bromofuran-2-yl)methyl]-4-methylpiperazine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A round-bottomed flask was charged with 1-((5-bromofuran-2-yl)methyl)-4-methylpiperazine (1.29 g, 4.88 mmol), and THF (20 mL). The solution was cooled to −78° C. in a dry ice/acetone bath. tert-Butyllithium (6.56 mL, 10.5 mmol; 1.6 M in pentane) was added, and the reaction mixture was stirred for 30 minutes. Tributylchlorostannane (1.12 mL, 4.15 mmol) was added the reaction mixture was stirred for 30 minutes. The reaction mixture was quenched by adding pH 7 phosphate buffer (20 mL) and warming to room temperature. The reaction mixture was extracted with EtOAc (50 mL), washed with brine (2×50 mL), dried over sodium sulfate, filter and concentrate. Purify by Biotage 40S (EtOAc). Isolated product (1.20 g, 52%) as a green oil. 1H NMR (CDCl3, 400 MHz) δ 6.47 (d, J=3.1 Hz, 1H), 6.21 (d, J=2.3 Hz, 1H), 3.62 (s, 2H), 2.50 (br s, 8H), 2.27 (s, 3H), 1.53 (m, 6H), 1.33 (m, 6H), 1.06 (m, 6H), 0.88 (m, 9H). was stirred for 30 minutes The reaction mixture was quenched by adding pH 7 phosphate buffer (20 mL) warming to room temperature The reaction mixture was extracted with EtOAc (50 mL) washed with brine (2×50 mL) dried over sodium sulfate filter concentrate Purify by Biotage 40S (EtOAc)

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

Procedure: A round-bottomed flask was charged with 1-methylpiperazine (2.02 mL, 18.2 mmol), 5-bromofuran-2-carbaldehyde (3.03 g, 17.3 mmol), and CH2Cl2 (30 mL). The reaction mixture was stirred for 30 minutes, and then sodium triacetoxy borohydride (4.77 g, 22.5 mmol) was added slowly over five minutes. The reaction mixture was stirred at room temperature for 4 hours, then poured into Na2CO3 (100 mL) and extracted with CH2Cl2 (2×100 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated to provide the product (2.35 g, 50%) as an orange solid. LRMS (esi pos) m/e 260 (M+1). The reaction mixture was stirred at room temperature for 4 hours extracted with CH2Cl2 (2×100 mL) The combined organic layers were dried over sodium sulfate filtered concentrated