Diisopropylethylamine → N-boc-l-valyl-l-valine methyl ester

Temperature

0 °C

N-tert-butoxycarbonyl L-valine (11.67 g, 53.71 mmol) was dissolved in DMF (50 mL) and the solution cooled to 0° C. (icebath). L-valine methyl ester hydrochloride (9.01 g, 53.7 mmol) was suspended in DMF (25 mL) and N,N-diisopropylethylamine (6.94 g, 53.7 mmol) added. The resulting solution was added to the solution of N-tert-butoxycarbonyl L-valine together with DMF (5 mL). HOBt hydrate (8.23 g, 53.7 mmol) and then EDC hydrochloride (11.33 g, 59.10 mmol) were added in portions together with an additional 30 mL DMF. The reaction mixture was stirred at 0° C. for 2 h 30 min after which the icebath was removed and stirring continued for 22 h 30 min at room temperature. The solvent was evaporated and the residue taken up in EtOAc (250 mL). The solution/suspension was washed with 1 M aqueous H2SO4 (3×100 mL), 7.5% (w/w) K2CO3 solution (3×100 mL) and saturated brine (100 mL). The solution was dried with anhydrous MgSO4 and the solvent evaporated affording a white solid (16.92 g, 95%); δH (200 MHz; d6-DMSO) 7.97 (1H, dd, J 8, NH(Val2)), 6.68 (1H, dd, J 9, NH(Val1)), 4.18 (1H, dd, J 8 and 6, CαH(Val2)), 3.86 (1H, dd, J 9 and 8, CαH(Val1)), 3.61 (3H, s, OCH3), 2.15-1.79 (2H, m, CH(CH3)), 1.37 (9H, s, (CH3)3), 0.91-0.80 (12H, m, CH3); δC (50 MHz, d6-DMSO): 171.7, 171.7, 155.3, 77.9, 59.4, 57.2, 51.5, 30.2, 29.8, 28.0, 19.0, 18.8, 18.1, 18.1

1. customwas removed
2. stirringstirring
3. waitcontinued for 22 h 30 min at room temperature
4. customThe solvent was evaporated
5. washThe solution/suspension was washed with 1 M aqueous H2SO4 (3×100 mL), 7.5% (w/w) K2CO3 solution (3×100 mL) and saturated brine (100 mL)
6. dry with materialThe solution was dried with anhydrous MgSO4
7. customthe solvent evaporated

ORD record

ord-c39fb1cf69d2444d8100c5f92f656f70

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09227995B2