Allyl acrylate → 3-Allyl 1-tert-butyl 4-oxopyrrolidine-1,3-dicarboxylate

Temperatur

3 °C

An ice-cooled (3° C.) stirred solution of N-boc-glycine, allyl ester (6.46 g, 30 mmol) in anhydrous tetrahydrofuran (60 mL) under nitrogen was treated with 1N lithium bis(trimethylsilylamide)/tetrahydrofuran (33 mL, 33 mmol) at a rate to keep pot temperature below 10° C., then stirred at 3° C. for 15 min and cooled (−40° C.). A solution of allyl acrylate (4.45 mL, 35 mmol) in anhydrous tetrahydrofuran (25 mL) was added dropwise, and the mixture allowed to reach room temperature, stirred 1 h, and refluxed for 2 h. The mixture was cooled to room temperature, quenched with glacial acetic acid (2.5 mL), and concentrated. The residual oil was dissolved in methylene chloride (300 mL) and the solution washed with water and saturated sodium bicarbonate (150 mL each), dried (Na2SO4), and concentrated. The residue was dissolved in minimum methylene chloride and loaded onto a silica gel column (350 mL volume) and eluted with 55:30:15 heptane/methylene chloride/ethyl acetate to afford 3-allyl 1-tert-butyl 4-oxopyrrolidine-1,3-dicarboxylate (5.07 g, 63%) as a colorless oil. NMR (CDCl3): δ 5.85-6.00 (m, 1 H), 5.20-5.40 (m, 2 H), 4.60-4.75 (m, 2 H), 4.20 (m, 1 H), 3.95-4.10 (m, 1 H), 3.87 (d, J=6.5 Hz, 1 H), 3.62 (t, J=8 Hz, 1 H), 1.48 (s, 9 H). MS (m+1): 270.4; MS (m−bu+1): 214.2.

1. customtemperature below 10° C.
2. temperaturecooled (−40° C.)
3. customto reach room temperature
4. stirringstirred 1 h
5. temperaturerefluxed for 2 h
6. temperatureThe mixture was cooled to room temperature
7. customquenched with glacial acetic acid (2.5 mL)
8. concentrationconcentrated
9. dissolutionThe residual oil was dissolved in methylene chloride (300 mL)
10. washthe solution washed with water and saturated sodium bicarbonate (150 mL each)
11. dry with materialdried (Na2SO4)
12. concentrationconcentrated
13. dissolutionThe residue was dissolved in minimum methylene chloride
14. washeluted with 55:30:15 heptane/methylene chloride/ethyl acetate

ORD-Eintrag

ord-da1fb768e9cd46fd915739e5ce927e90

Quelldatensatz

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09440995B2