H-NVA-OME HCL

White to off-white powder

L-Norvaline (160 g, 1.34 mol) is dissolved in a 28.5percent methanolic solution of HC1 (278 g) and diluted with methanol (500 ml). The solution is refluxed under inert atmosphere for 6 hours. When the reaction has terminated, the solvents are distilled by coevaporating with toluene. The residue is treated at 50°C with tert-butyl methyl ether (800 ml). The suspension obtained is left under stirring at room temperature and then filtered, and the white solid obtained is washed with tert-butyl methyl ether to obtain 216 g of L-norvaline methyl ester hydrochloride with a yield of 97percent.HCL 3. 0g [(25.] 6 mmol, 1.0 Eq. ) of [L-NORVALINE] was dissolved in 50.0 mL of methanol and cooled to 0 [°C.] This was saturated with [HCI] gas and gradually allowed to warm to room temperature. After 14 hours the solvent was removed and the solid was dried overnight in a [DESSICATOR] with phosphorous [PENTACHLORIDE.] 3.6g (86percent) of a white solid was obtained. (MS: 126. [9/] [[P-APOS;])] (H'NMR in [CDCI3] : 0.95, 3H t, (J=382 Hz), 1.46, 2H m, (J=587 Hz), 2.01, 2H m, (J=806 Hz), 3 78, 3H s, [(J=1512] Hz), 4.05, 1H m, [(J=1622.] 459 Hz), 8.74, 2H brds, (J=3495 Hz))L-Norvaline (160 g, 1.34 mol) is dissolved in a 28.5percent methanolic solution of HC1 (278 g) and diluted with methanol (500 ml). The solution is refluxed under inert atmosphere for 6 hours. When the reaction has terminated, the solvents are distilled by coevaporating with toluene. The residue is treated at 50°C with tert-butyl methyl ether (800 ml). The suspension obtained is left under stirring at room temperature and then filtered, and the white solid obtained is washed with tert-butyl methyl ether to obtain 216 g of L-norvaline methyl ester hydrochloride with a yield of 97percent.HCL 3. 0g [(25.] 6 mmol, 1.0 Eq. ) of [L-NORVALINE] was dissolved in 50.0 mL of methanol and cooled to 0 [°C.] This was saturated with [HCI] gas and gradually allowed to warm to room temperature. After 14 hours the solvent was removed and the solid was dried overnight in a [DESSICATOR] with phosphorous [PENTACHLORIDE.] 3.6g (86percent) of a white solid was obtained. (MS: 126. [9/] [[P-APOS;])] (H'NMR in [CDCI3] : 0.95, 3H t, (J=382 Hz), 1.46, 2H m, (J=587 Hz), 2.01, 2H m, (J=806 Hz), 3 78, 3H s, [(J=1512] Hz), 4.05, 1H m, [(J=1622.] 459 Hz), 8.74, 2H brds, (J=3495 Hz))11.6 g (50.0 mmol) N-tert-butoxycarbonyl-L-isoleucine, 16.1 g (50.0 mmol) TBTU and 25.5 ml (150 mmol) DIPEA were dissolved in 230 ml THF. 8.4 g (50.0 mmol) L-2-aminovalericacid-methylester-hydrochloride were added and the reaction was stirred at room temperature overnight. The mixture was extracted with 20% KHSO4 solution and water. The organic phase was separated with an isolute phase separator and evaporated. The residue was purified by MPLC (silica gel, dichloromethane/methanol=95:5) to yield 15.9 g (92%) 1-f ES-MS (M+H)+345