N-methyl-2-pyrrolidone → 1,1-Dimethylethyl 5-chloro-6-methyl-3-pyridinecarboxylate
Reaction equation
[C:1]([O:5][C:6](=[O:15])[C:7]1[CH:12]=[C:11]([Cl:13])[C:10](Cl)=[N:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:16]N1C(=O)CCC1.C[Mg]Cl.C[Mg]Br>C1COCC1>[C:1]([O:5][C:6](=[O:15])[C:7]1[CH:12]=[C:11]([Cl:13])[C:10]([CH3:16])=[N:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
To a solution of 5,6-dichloronicotinic acid tert.-butyl ester (3.37 g, 13.6 mmol), Fe(acac)3 (719 mg, 2.04 mmol) and NMP (1.95 mL, 20 mmol) in THF (300 mL), a solution of methylmagnesium chloride in THF (3 M, 5.4 mL, 16.3 mmol) is slowly added at −78° C. The brown solution turns turbid and black. Stirring is continued for 1 h at −75° C. before it is warmed to 0° C. The reaction is incomplete and the mixture is cooled again at −70° C. A further batch of methylmagnesium bromide in THF (3 M, 5.4 mL, 16.3 mmol) is slowly added at −70° C. The dark green mixture is slowly warmed to −20° C. and carefully quenched with 0.7 N aq. HCl (150 mL). The mixture is extracted with diethyl ether (5×60 mL). The combined org. extracts are dried over Na2SO4, filtered and evaporated to give crude 5-chloro-6-methyl-nicotinic acid tert.-butyl ester as a yellow oil (4.66 g); LC-MS: tR=1.03 min, [M+1]+=228.22.
Workup
- temperaturethe mixture is cooled again at −70° C
- temperatureThe dark green mixture is slowly warmed to −20° C.
- customcarefully quenched with 0.7 N aq. HCl (150 mL)
- extractionThe mixture is extracted with diethyl ether (5×60 mL)
- dry with materialextracts are dried over Na2SO4
- filtrationfiltered
- customevaporated
Sources & evidence
- ORD record
- ord-e5137dc88d1f41e09d4398789d2e5532
- Source dataset
- uspto-grants-2013_12
- Patent number
- US08598208B2
Reaction notes
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