Diisopropylethylamine → HCID 87403496, compound

Participants

Reaction Conditions

Reaction Steps

N-tert-butoxycarbonyl α,α-dimethylglycine 1 (3.20 g, 15.7 mmol) and α,α-dimethylglycyl α,α-dimethylglycine methyl ester trifluoroacetate 5 (4.98 g, 15.7 mmol) were dissolved in DMF (40 mL). N,N-Diisopropylethylamine (2.06 g, 15.9 mmol) and HOBt hydrate (2.41 g, 15.7 mmol) were added together with more DMF (10 mL). The solution was cooled to 0° C. (ice bath) and EDC hydrochloride (3.32 g, 17.3 mmol) added in portions together with additional DMF (10 mL). The reaction mixture was stirred for 15 min at 0° C., after which the ice bath was removed and stirring continued for 43 h at room temperature. The solvent was evaporated and the residue taken up in EtOAc (150 mL). The solution was washed with 1 M aqueous H2SO4 (3×50 mL), 7.5% (w/w) K2CO3 solution (3×50 mL) and saturated brine (50 mL). After dilution with EtOAc (100 mL) the solution was dried with anhydrous MgSO4 and the solvent evaporated affording an off-white solid (3.20 g, 52%), with spectral characteristics in accordance with literature data6; 1H NMR (200 MHz, DMSO-d6) δ 7.59 (s, 2H, NH(Aib2)/NH(Aib3)), 7.21 (s, 1H, NH(Aib1)), 3.53 (s, 3H, OCH3), 1.41 (s, 9H, (CH3)3), 1.33 (s, 6H, CH3), 1.28 (s, 6H, CH3), 1.25 (s, 6H, CH3); 13C NMR (75 MHz, DMSO-d6) δ 174.4, 173.8, 173.2, 155.1, 78.7, 55.8, 55.4, 54.9, 51.6, 28.1, 24.8, 24.6, 24.6; HRMS (m/z): [M+Na]+ calcd. for C18H33N3O6Na, 410.2267. found, 410.2269; Anal. Calcd. for C18H33N3O6: C, 55.80; H, 8.58; N, 10.84. Found: C, 55.9; H, 8.7; N, 11.0.

Provenance & Evidence