Dimethylformamide → Ethyl 6-chloro-5-cyanonicotinate
Reaction equation
[C:1]([C:3]1[C:4](O)=[N:5][CH:6]=[C:7]([CH:13]=1)[C:8]([O:10][CH2:11][CH3:12])=[O:9])#[N:2].CN(C=O)C.O=S(Cl)[Cl:22]>>[Cl:22][C:4]1[C:3]([C:1]#[N:2])=[CH:13][C:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:6][N:5]=1Participants
4
Procedure
To a solution of 222 mg (1.16 mmol) of ethyl 5-cyano-6-hydroxynicotinate (from Step A) in 5 mL of SOCl2 was added 500 μL of DMF. After refluxing overnight, the mixture was cooled to rt and concentrated. The residue was dissolved in EtOAc (20 mL) and washed with brine (10 mL), saturated NaHCO3 (10 mL), and brine (10 mL), dried over Na2SO4, and concentrated. Chromatography on a Biotage 40M cartridge using 1:9 v/v EtOAc/hexanes gave 145 mg of the title compound: 1H NMR (500 MHz, CDCl3) δ 1.44 (d, J=7.1, 3H), 4.46 (q, J=7.1, 2H), 8.58 (d, J=2.1, 1H), 9.15 (d, J=2.1, 1H).
Workup
- temperatureAfter refluxing overnight
- concentrationconcentrated
- dissolutionThe residue was dissolved in EtOAc (20 mL)
- washwashed with brine (10 mL), saturated NaHCO3 (10 mL), and brine (10 mL)
- dry with materialdried over Na2SO4
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-57bf52f7021f455581024ab36c23e1be
- Source dataset
- uspto-grants-2009_10
- Patent number
- US07605171B2
Reaction notes
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