Water → HCID 46926793, compound

Participants

Reaction Steps

Lithium hydroxide monohydrate (14.3 mg, 0.342 mmol) was added to a solution of methyl 2,2-dimethyl-3-(5-(4-(phenylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyridin-2-yloxy)propanoate B-3 (ca. 62.0 mg, 0.114 mmol) in 1:1:1 tetrahydrofuran:water:methanol (1.14 mL) at room temperature. After 12 h of vigorous stirring at room temperature, lithium hydroxide monohydrate (14.3 mg, 0.342 mmol) was added, and the reaction mixture was heated at 65° C. under microwave irradiation for 30 mins. The clear solution was then quenched with a 1 N aqueous solution of hydrogen chloride (1.0 mL) and concentrated to dryness under reduced pressure. The crude residue was purified by flash column chromatography on C18 reverse phase (water:acetonitrile gradient with 0.05% formic acid) to give white crystalline 2,2-dimethyl-3-(5-(4-(phenylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyridin-2-yloxy)propanoic acid B-4 (36.6 mg, Yield=72% over 2 steps). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.23 (s, 6H), 3.88 (t, J=4.10 Hz, 2H), 4.28 (s, 2H), 4.30 (t, J=4.10 Hz, 2H), 6.86 (d, J=8.51 Hz, 1H), 7.01 (dt, J=1.10, 7.41 Hz, 1H), 7.16-7.21 (m, 2H), 7.29 (t, J=7.72 Hz, 2H), 7.50 (d, J=8.20 Hz, 2H), 7.60 (d, J=8.51 Hz, 1H), 7.98 (br d, J=8.51 Hz, 1H), 8.44 (s, 1H), 9.16 (s, 1H), 12.37 (br s, 1H); MS (ESI) [M+1]+ 448.

Provenance & Evidence