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

HRID 61352

Reaction equation

HRID 61352 reaction equation
[C:1]([NH:8][CH2:9][C:10]([O:12]CC=C)=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C[Si]([NH-])(C)C.C[Si]([NH-])(C)C.[Li+].[Li+].O1CCCC1.[C:33]([O:37][CH2:38][CH:39]=[CH2:40])(=[O:36])[CH:34]=[CH2:35]>O1CCCC1>[O:12]=[C:10]1[CH2:9][N:8]([C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH2:35][CH:34]1[C:33]([O:37][CH2:38][CH:39]=[CH2:40])=[O:36]

Participants

5

Reactant 3

HCID 13835Allyl acrylateHCID 22157668Prop-2-en-1-yl 2-{[(tert-butoxy)carbonyl]amino}acetateHCID 86665784Lithium bis(trimethylsilylamide) tetrahydrofuran

Product 1

HCID 675170133-Allyl 1-tert-butyl 4-oxopyrrolidine-1,3-dicarboxylateYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
3 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-da1fb768e9cd46fd915739e5ce927e90
Source dataset
uspto-grants-2016_09
Patent number
US09440995B2

Linked notes

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