Carbamate → tert-butyl (S)-2-(4-(4-(thiophen-3-yl)phenethyloxy)phenylcarbamoyl)-1-hydroxypropan-2-ylcarbamate

Participants

Reaction Steps

The starting material, 2-(4-(thiophen-3-yl)phenyl)ethanol, was synthesized as follows: In a sealed vessel was combined 2-(4-bromophenyl)ethanol (70 μL), 4,4,5,5-tetramethyl-2-(thiophen-3-yl)-1,3,2-dioxaborolane (126 mg), K2CO3 (207 mg), catalytic Pd(PPh3)4, 4.5 mL THF, and 0.5 mL H2O. The vessel was heated in an oil bath at 60° C. overnight. The reaction mixture was diluted with water and DCM. The organic layer was concentrated to yield 2-(4-(thiophen-3-yl)phenyl)ethanol (80 mg) as a solid white product. 80 mg tert-butyl (S)-2-(4-(4-(thiophen-3-yl)phenethyloxy)phenylcarbamoyl)-1-hydroxypropan-2-ylcarbamate was synthesized following the general procedure employing 2-(4-(thiophen-3-yl)phenyl)ethanol (200 mg), N-(Boc)-α-methylserine (175 mg), HATU (375 mg), and DIPEA (430 uL). MS (ESI, M+Na+)=519. 2.6 mg of the phosphate was then synthesized from the carbamate (40 mg) as a solid white solid. MS (ESI, M+H+)=477; 1H NMR (400 MHz, DMSO-d6), 9.96 (br s, 1H), 7.81 (m, 1H), 7.65 (m, 3H), 7.5 (m, 3H), 7.3 (m, 2H), 6.9 (m, 2H), 4.28 (m, 1H), 4.17 (m, 2H), 4.06 (m, 1H), 3.04 (t, 2H), 1.48 (s, 3H).

Provenance & Evidence