Lithium borohydride → HCID 58827198, compound

Participants

Reaction Conditions

Reaction Steps

5-(4-Cyano-2-methoxyphenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazole-5-carboxylic acid methyl ester (0.100 g, 0.336 mmol) is dissolved in THF (3 mL) and cooled to −10° C. A THF solution of lithium borohydride (0.08 mL, 2 M) is then added. The solution is removed from the cold bath and allowed to warm to room temperature before being heated to 40° C. at which time additional lithium borohydride (0.08 mL, 2 M) is added. The solution is maintained at that temperature for 1.5 h before being allowed to cool to room temperature and being quenched by the addition of 1 M HCl. Following aqueous workup the residue is warmed to 80° C. in ethanolamine/CH3CN (1:3) for 1 h. The solution is then concentrated and the residue purified via prep HPLC (reversed phase; 5-100% CH3CN/H2O and 0.1% TFA). Conversion to the free base provided 4-(5-hydroxymethyl-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-methoxybenzonitrile as a white solid. MS (ESI) m/z 270.1 (M+H); 1H NMR (400 MHz, CDCl3) δ ppm 2.55-2.67 (m, 1H), 2.78-2.96 (m, 3H), 3.91 (s, 3H), 4.10 (d, J=11.6 Hz, 1H), 4.46 (d, J=11.6 Hz, 1H), 6.57 (d, J=8.3 Hz, 1H), 6.73 (s, 1H), 7.13-7.18 (obs m, 1H), 7.16 (s, 1H), 7.52 (s, 1H).

Provenance & Evidence