Water → 6-Bromo-2-(piperidin-4-ylmethyl)benzo[d]oxazole

Participants

Reaction Steps

Hexamethyldisiloxane (1.068 g, 6.58 mmol) was added to a solution of P2O5 (0.786 g, 5.54 mmol) in dry 1,2-Dichloroethane (2.9 mL) under argon and then heated to reflux for 10 min. A solution of tert-butyl 4-(2-(4-bromo-2-hydroxyphenylamino)-2-oxoethyl)piperidine-1-carboxylate (0.41 g, 0.992 mmol) in 1,2-Dichloroethane (2.9 mL) was added and the mixture was heated to reflux for 3 h. The mixture was poured into cool water (5 mL), extracted with CH2Cl2 (3×3 mL). The organic layers were discarded. The aqueous layer and the remaining solid were brought to pH=12 using aqueous NaOH (1 N). The mixture was extracted with CH2Cl2 (3×6 mL). The combined organic layers were dried (K2CO3), filtered, and concentrated to afford desired product as an orange oil (0.133 g, HPLC purify 95%, 43% yield). 1H NMR (500 MHz, chloroform-d) δ ppm 7.65 (d, J=1.7 Hz, 1H), 7.48-7.56 (m, 1H), 7.38-7.46 (m, 1H), 3.01-3.15 (m, 2H), 2.80-2.89 (m, 2H), 2.63 (td, J=12.2, 2.1 Hz, 2H), 1.96-2.14 (m, J=15.0, 7.7, 7.6, 3.6, 3.4 Hz, 1H), 1.74 (d, J=12.7 Hz, 2H), 1.57 (br. s., 1H), 1.20-1.36 (m, 2H). LCMS (m/z)=295 (M+H)+.

Provenance & Evidence