Reaction #6530

Reaction equation

allyl bromide

Methyl 2-(nicotinoyl)acetate

sodium

Allyl bromide

→

methyl-2-nicotinoyl-4-pentenoate

Solvents

methanol

Conditions

Workup

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITwas continued overnight
3. 3
   workup.STIRRINGthe mixture was stirred for 48 hours
4. 4
   Concentrationconcentrated
5. 5
   OtherThe residual oil was partitioned between water and ether
6. 6
   Extractionthe aqueous layer was extracted three times with ether
7. 7
   WashThe combined extracts were washed with saturated brine
8. 8
   Dryingdried (MgSO4)
9. 9
   Concentrationconcentrated
10. 10
    OtherThe residue was purified by flash column chromatography
11. 11
    Washeluting with a mixture of petroleum ether (b.p. 60°-80°) and ethyl acetate (1:1

Procedure

Methyl 2-(nicotinoyl)acetate (17.9 g, prepared by the method of E. Wenkert el al. J. Org. Chem., 1983, 48, 5006) was added under argon to a solution of sodium metal (2.3 g) in methanol (200 ml) and the resulting mixture was stirred at 25° C. for 30 mins. Allyl bromide (12.0 g) was then added and stirring was continued overnight. A further amount (about 2 g) of allyl bromide was added, the mixture was stirred for 48 hours, and then concentrated. The residual oil was partitioned between water and ether and the aqueous layer was extracted three times with ether. The combined extracts were washed with saturated brine, dried (MgSO4) and concentrated. The residue was purified by flash column chromatography, eluting with a mixture of petroleum ether (b.p. 60°-80°) and ethyl acetate (1:1, v/v) to give methyl-2-nicotinoyl-4-pentenoate (A) as a pale yellow oil (13.8 g); NMR 2.6-2.9 (2H,m), 3.7 (3H,s), 4.4 (1H,m), 4.9-5.2 (2H,m), 5.5-6.0 (1H,m), 7.2-7.5 (1H,m), 8.1-8.3 (1H,m), 8.7-8.8 (1H,m) and 9.1-9.2 (1H,m).

Source