Acetic Acid → Ethyl 2-bromo-5-methylpyridine-3-carboxylate
Reaction equation
[CH:1](=[C:4]([C:8]#[N:9])[C:5]([O-:7])=[O:6])[CH2:2][CH3:3].[CH3:10]OC(OC)N(C)C.[BrH:18].[C:19](O)(=O)[CH3:20]>>[Br:18][C:8]1[N:9]=[CH:3][C:2]([CH3:10])=[CH:1][C:4]=1[C:5]([O:7][CH2:19][CH3:20])=[O:6]Participants
Procedure
Following the procedure of Baldwin, et al., J. Org. Chem., 43(12), 2529 (1978), 5.70 g of 2-propylidenecyanoacetate (37 mmol) was reacted with 4.43 g of dimethylformamide dimethylacetal (37 mmol). The resulting adduct was reacted with hydrogen bromide in acetic acid to give ethyl 2-bromo-5-methylnicotinate. The crude bromide was dissolved in 30 mL of ethanol, 15 mL of n-propylamine was added, and the resultant solution was heated in a sealed tube at 100° C. for 5 hours. After cooling to ambient temperature, the volatiles were removed in vacuo and the residue was chromatographed on silica gel eluting with 20% ethyl acetate in hexanes to afford 3.3 g (40% overall) of the title product. 1H NMR (CDCl3, 300 MHz) δ 1.00 (t, J=7 Hz, 3H), 1.40 (t, J=7 Hz, 3H), 1.65 (sextet, J=7 Hz, 2H), 2.44 (s, 3H), 3.43 (dt, J=5 Hz, 7 Hz, 2H), 4.36 (q, J=7 Hz, 2H), 6.34 (d, J=5 Hz, 1H), 7.68 (bs, 1H), 8.06 (d, J=5 Hz, 1H). MS (DCl/NH3) m/e 223 (M+H)+.
Sources & evidence
- ORD record
- ord-98aec0e493e2484284850b06481e015e
- Source dataset
- uspto-grants-1993_10
- Patent number
- US05250548
Reaction notes
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