Methyl Nicotinate → 1-(But-1-enyl)-3-nicotinoyl-pyrrolidin-2-one

HRID 389162

Reaction equation

HRID 389162 reaction equation
[CH:1]([N:5]1[CH2:9][CH2:8][CH2:7][C:6]1=[O:10])=[CH:2][CH2:3][CH3:4].[C:11](OC)(=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[N:14][CH:13]=1>CN(C)C=O>[CH:1]([N:5]1[CH2:9][CH2:8][CH:7]([C:11](=[O:18])[C:12]2[CH:17]=[CH:16][CH:15]=[N:14][CH:13]=2)[C:6]1=[O:10])=[CH:2][CH2:3][CH3:4]

Participants

4

Reactant 2

HCID 7151Methyl NicotinateHCID 5801701-(But-1-enyl)pyrrolidin-2-one

Product 1

HCID 681592951-(But-1-enyl)-3-nicotinoyl-pyrrolidin-2-oneYield 94.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
90 °C

Procedure

Sodium hydride (8.63 g, 0.36 mol of 60% dispersion in a mineral oil) was washed with toluene to remove mineral oil. To this 20 ml of dimethylformamide (DMF), 1-(but-1-enyl)pyrrolidin-2-one (25 g, 0.1798 mol) and a solution of methyl nicotinate (20.94 g, 0.152 mol) in 15 ml of DMF were added. The reaction mixture was heated at 90° C. for 2 hrs. DMF was partially removed under reduced pressure, 50 ml water added, further cooled to 0-10° C. and pH adjusted to 7 using HCl. The reaction mixture was extracted with ethyl acetate and dried over Na2SO4. After removing the solvent under reduced pressure a yellow solid was obtained, which on recrystallisation with diisopropyl ether gave 1-(but-1-enyl)-3-nicotinoyl-pyrrolidin-2-one (II, 35.1 g, 94% yield), 95% HPLC, M.R: 65-66° C. 1H NMR (CDCl3): δ 9.3 (1H, d), 8.8 (1H, d), 8.41 (1H, dt), 7.4 (1H, m), 6.76 (1H, d), 5.0 (1H, m), 4.5 (1H, m), 3.57-3.67 (2H, m), 2.7 (1H, m), 2.3 (1H, m), 2.0 (2H, m), and 1.0 (3H, t). 13C-NMR (CDCl3): δ 194.4, 167.1, 153.7, 150.4, 137.0, 134.4, 131.2, 123.3, 114.9, 51.7, 44.2, 23.2, 22.3, and 14.26. IR: 2966, 2937, 2855, 2847, 1631, 1613, 1489 Cm−1.

Workup

  1. washSodium hydride (8.63 g, 0.36 mol of 60% dispersion in a mineral oil) was washed with toluene
  2. customto remove mineral oil
  3. customDMF was partially removed under reduced pressure, 50 ml water
  4. additionadded
  5. temperaturefurther cooled to 0-10° C.
  6. extractionThe reaction mixture was extracted with ethyl acetate
  7. dry with materialdried over Na2SO4
  8. customAfter removing the solvent under reduced pressure a yellow solid
  9. customwas obtained
  10. customwhich on recrystallisation with diisopropyl ether

Sources & evidence

ORD record
ord-700ca42984214e05801c48263509ec2f
Source dataset
uspto-grants-2013_02
Patent number
US08378110B1

Linked notes

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