4-Methylmorpholine → HCID 14039196, compound

Participants

Reaction Steps

A solution of 1.7 g (0.0075 mol) of Boc-Leucine in 30 ml of dry tetrahydrofuran was cooled to -5° C. and 0.99 g (0.0089 mol) of N-methylmorpholine and 1.0 g (0.0075 mol) of isobutyl chloroformate were added and stirred for 1 h. A solution of compound 1 (3.0 g, 0.0075 mol) in 10 ml of dioxane:water (7:3) (v/v) containing (0.0089 mol) 0.909 g of triethylamine was added. The mixture was stirred for 3 at ambient temperature, approximately 20 ml water was added and the tetrahydrofuran was evaporated in vacuo. The resulting oil was extracted with ethyl acetate (80 ml) and the pooled extracts were washed sequentially with 1N-hydrochloric acid, sat'd sodium bicarbonate solution, sat'd sodium chloride solution and dried over anhydrous Na2SO4. The solvent was removed in vacuo yielding an oil: 2.9 g (0.007 mol, yield 94%); homogeneous on TLC Rf (A) 0.91, Rf (B) 0.70). The resulting ester was dissolved in 20 ml of methanol and 20 ml of 1N sodium hydroxide was added. The mixture was stirred for 3 h at ambient temperatures and then concentrated in vacuo. The aqueous solution was acidified with 4N-hydrochloric acid while stirring on ice and then extracted with ethyl acetate. The pooled extracts were washed with sat'd sodium chloride, dried over sodium sulfate and evaporated in vacuo to yield a clear oil: (2.7 g, 95% yield; Rf (A) 0.79, Rf (B) 0.83; [α]D25 -22.2° (c 1, MeOH); H1NMR (CDCl3) δ: 0.95 (m, 7H, H3C--CH--CH3), 1.17(m, 2H, CH2) 1.4 (s, 9H, Boc), 2.15(m, 1H, NH--CH--C(O)) 4.05(d, 1H, CH--COH), 4.15(d, 1H, CH--COOH), 4.6 (s, 1H, OH, exchanged by D2O), 4.75(d, 1H, C(O)--NH, exchanged by D2O) 4.8(d, 1H, C(O)--NH, exchanged D2O, 7.3(s, 5H, ArH), 9.5(b, 1H, COOH) Anal. Calcd for C20H30O6N2 : C 60.91, H, 7.61N, 7.10., Found: C, 60.89H, 7.62, N, 7.08.

Provenance & Evidence