N-methyl-2-pyrrolidone → HCID 67026912, compound

HRID 1908763Notes

Reaction equation

HRID 1908763 reaction equation
[C:1]([O:5][C:6](=[O:15])[C:7]1[CH:12]=[C:11](Cl)[C:10]([CH3:14])=[N:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2].CN1C(=O)CCC1.[CH2:23]([Mg]Br)[CH:24]([CH3:26])[CH3:25].C[Mg]Br>C1COCC1>[C:1]([O:5][C:6](=[O:15])[C:7]1[CH:12]=[C:11]([CH2:23][CH:24]([CH3:26])[CH3:25])[C:10]([CH3:14])=[N:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 670268831,1-Dimethylethyl 5-chloro-6-methyl-3-pyridinecarboxylateHCID 178418573HCID 178418573, compoundHCID 178418816HCID 178418816, compound

Product 1

HCID 67026912HCID 67026912, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

5-Chloro-6-methyl-nicotinic acid tert.-butyl ester (3.09 g, 13.5 mmol), Fe(acac)3 (719 mg, 2.04 mmol) and NMP (1.95 mL, 20 mmol) are dissolved in THF (3 M, 500 mL) and cooled at −78° C. A solution of isobutylmagnesium bromide in THF (2 M, 13.6 mmol) is slowly added at −75° C. The brown solution turns turbid and yellow. Stirring is continued for 1 h at −75° C. before it is slowly warmed to rt. The reaction is incomplete, further Fe(acac)3 (719 mg, 2.04 mmol) is added and the mixture is cooled again at −70° C. Further methylmagnesium bromide in THF (2 M, 13.6 mmol) is slowly added at −70° C. The dark green mixture is slowly warmed to rt and stirred for 15 h. The mixture is carefully quenched with 0.7 N aq. HCl (150 mL). The mixture is extracted with EA (6×60 mL). The combined org. extracts are dried over Na2SO4, filtered and evaporated. The residue is purified by reversed phase MPLC to give 6-methyl-5-isobutyl-nicotinic acid tert.-butyl ester as black oil (0.50 g); LC-MS: tR=0.84 min, [M+1]+=250.14.

Workup

  1. temperatureis slowly warmed to rt
  2. temperaturethe mixture is cooled again at −70° C
  3. temperatureThe dark green mixture is slowly warmed to rt
  4. stirringstirred for 15 h
  5. customThe mixture is carefully quenched with 0.7 N aq. HCl (150 mL)
  6. extractionThe mixture is extracted with EA (6×60 mL)
  7. dry with materialextracts are dried over Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue is purified by reversed phase MPLC

Sources & evidence

ORD record
ord-fa263db0dfe1458988dd2b088cb626c0
Source dataset
uspto-grants-2013_12
Patent number
US08598208B2

Reaction notes

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