Triethylamine → (2S,4R)-methyl 1-((2S,3R)-2-((tert-butoxycarbonyl)amino)-3,5-dimethylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylate

O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (“HATU”, 31.7 g, 83.0 mmol) was added to a solution of (2S,4R)-methyl 4-hydroxypyrrolidine-2-carboxylate HCl salt (16.7 g, 92.0 mmol), (3R)-2-((tert-butoxycarbonyl)amino)-3,5-dimethylnon-8-enoic acid (25 g, 83 mmol) and NEt3 (35 mL, 250 mmol) in CH2Cl2 (250 mL) and the solution was stirred at room temperature for 16 h. The reaction solution was transferred to a reparatory funnel and was washed with aqueous 1N HCl (3×) and then brine. The organics were dried over MgSO4, filtered and concentrated in vacuo. The crude material was purified via silica gel chromatography (hexane:acetone 80:20 to 40:60) to afford the desired product (2S,4R)-methyl 1-((2S,3R)-2-((tert-butoxycarbonyl)amino)-3,5-dimethylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylate (10.8 g, 30% yield), MS: MS m/z 427.2 (M++1) and the undesired product (2S,4R)-methyl 1-((2R,3R)-2-((tert-butoxycarbonyl)amino)-3,5-dimethylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylate (12 g, 34% yield), MS: MS m/z 427.2 (M++1).

1. customThe reaction solution was transferred to a reparatory funnel
2. washwas washed with aqueous 1N HCl (3×)
3. dry with materialThe organics were dried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe crude material was purified via silica gel chromatography (hexane:acetone 80:20 to 40:60)

ORD 기록

ord-237777a871544644b20b715a3ab97c6f

출처 데이터셋

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09334279B2