Diisopropylethylamine → HCID 86685806, compound

Participants

Reaction Steps

To a slurry of (3R)-2-((tert-butoxycarbonyl)amino)-3,7-dimethylnon-8-enoic acid (6.5 g, 21.7 mmol), L-4-hydroxyproline methyl ester hydrochloride (3.9 g, 21.7 mmol) and O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (8.36 g, 21.7 mmol) in DCM (50 mL) at 0° C., N,N-diisopropylethylamine (11.5 mL, 66.6 mmol) was added dropwise. The resulting light yellow mixture was stirred at rt overnight, washed with 1M HCl (35 ml) and brine, dried over Na2SO4, filtered, concentrated in vacuo. The residual oil (12 g) was purified by conventional column chromatography (60-120 g silica gel column), eluted with 4%˜8% IPA-Hexane to afford the desired product (2S,4R)-methyl 1-((2S,3R)-2-(tert-butoxycarbonylamino)-3,7-dimethylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylate (9a, 4.3 g, 46% yield) as a white foam and the undesired diastereomer (2S,4R)-methyl 1-((2R,3R)-2-(tert-butoxycarbonylamino)-3,7-dimethylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylate (9b, 1.9 g, 20% yield) as a viscous oil. 1H NMR (400 MHz, CDCl3): δ ppm 5.73-5.64 (m, 1H), 5.19-5.17 (m, 1H), 4.97-4.88 (m, 2H), 4.70-4.66 (t, J=8.4 Hz, 1H), 4.53 (bs, 1H), 4.29-4.25 (m, 1H), 3.99-3.96 (d, J=10.8 Hz, 3H), 3.72 (s, 3H), 3.70-3.66 (m, 1H), 2.34-2.11 (m, 1H), 2.10-2.00 (m, 2H), 1.85-1.81 (m, 1H), 1.49-1.41 (m, 9H), 1.39-1.14 (m, 3H), 0.98-0.86 (m, 7H) MS: MS m/z 427.2 (M++1).

Provenance & Evidence