Diisopropylethylamine → HCID 14805857, compound

Participants

Reaction Conditions

Reaction Steps

Aminoisobutyric acid methyl ester hydrochloride 2 (11.44 g, 74.47 mmol) and N,N-diisopropylethylamine (9.63 g, 74.5 mmol) were dissolved in DMF (400 mL) and the solution added to solid N-tert-butoxycarbonyl α,α-dimethylglycine (15.14 g, 74.49 mmol). The solution/suspension was cooled to 0° C. (icebath) and HOBt hydrate (11.41 g, 74.51 mmol) and then EDC hydrochloride (15.71 g, 81.95 mmol) added together with more DMF (100 mL). The reaction mixture was stirred for 30 min at 0° C., after which the icebath was removed and stirring continued for 66 h at room temperature. The solvent was evaporated and the residue taken up in EtOAc (500 mL). The solution was washed with 2 M HCl (3×175 mL), 7.5% (w/w) K2CO3 solution (3×175 mL) and saturated brine (175 mL). The solution was dried with anhydrous MgSO4 and the solvent evaporated affording a slightly yellowish solid (17.04 g). The solid (16.72 g) was washed with hexane (4×70 mL) affording an off-white solid (14.72 g, 67%), with spectral characteristics in accordance with literature data2,3; 1H NMR (200 MHz; DMSO-d6) δ 7.57 (s, 1H, NH(Aib2)), 6.63 (br s, 1H, NH(Aib1)), 3.55 (s, 3H, OCH3), 1.37 (s, 9H, (CH3)3), 1.34 (s, 6H, CH3), 1.28 (s, 6H, CH3); 13C NMR (75 MHz, DMSO-d6) δ 174.5, 174.0, 154.1, 78.0, 55.5, 55.1, 51.7, 28.1, 24.8, 24.7; HRMS (m/z): [M+Na]+ calcd. for C14H26N2O5Na, 325.1739. found, 325.1746; Anal. Calcd. for C14H26N2O5: C, 55.61; H, 8.67; N, 9.26. Found: C, 55.9; H, 8.7; N, 9.2.

Provenance & Evidence