Reaction Steps
N-tert-butoxycarbonyl O-allyl L-seryl α,α-dimethylglycyl L-valine methyl ester 12 (8.56 g, 19.3 mmol) was dissolved in THF (150 mL). The solution was cooled to 0° C. (icebath). LiOH monohydrate (0.891 g, 21.2 mmol) was dissolved in de-ionized water (75 mL) and the solution cooled to 0° C. The solution was added dropwise to the solution of 12 over 20 min. The reaction mixture was stirred for an additional 2 h 40 min before solid NaHCO3 (3.24 g, 38.6 mmol) was added. The mixture was stirred for 5 min and the bulk of THF evaporated. The solution was diluted with water (150 mL), washed with Et2O (2×150 mL), acidified to pH 2 by addition of 2 M aqueous H2SO4 and extracted with EtOAc (3×300 mL). The combined organic fractions were dried with anhydrous MgSO4 and the solvent evaporated affording the title compound as a white solid (7.30 g, 88%); δH (300 MHz; d6-DMSO) 12.62 (1H, br s, COOH), 8.01 (1H, s, NH(Aib)), 7.12 (1H, d, J 9, NH(Val)), 6.85 (1H, d, J 8, NH(Ser(All))), 5.92-5.79 (1H, m, CH═CH2), 5.29-5.21 (1H, m, CH═CHH), 5.15-5.10 (1H, m, CH═CHH), 4.19-4.10 (2H, m, CαH(Ser(All))/CαH(Val)), 3.94 (2H, dt, J 1 and 5, CH2CH═CH2), 3.57-3.45 (2H, m, CH2), 2.08-1.97 (1H, m, CH(CH3)2), 1.38 (12H, s, CH3(Aib)/(CH3)3), 1.35 (3H, s, CH3(Aib)), 0.84 (3H, d, J 7, CH3(Val)), 0.81 (3H, d, J 7, CH3(Val)); δC (75 MHz; d6-DMSO): 173.6, 172.7, 169.5, 155.1, 134.9, 116.3, 78.2, 70.9, 69.5, 57.0, 56.1, 54.4, 30.1, 28.1, 25.7, 23.8, 19.0, 17.8; m/z (ESI) 452.2357 ([M+Na]+; C20H35N3O7Na requires 452.2372)
