Carbon Dioxide → HCID 68106369, compound

HRID 2403613Notes

Reaction equation

HRID 2403613 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH3:21])[C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.C([Li])CCC.[C:27](=[O:29])=[O:28].Cl>C1COCC1.O>[C:17]([O:16][C:14]([N:11]1[CH2:12][CH2:13][N:8]([C:5]2[C:4]([CH3:21])=[CH:3][C:2]([C:27]([OH:29])=[O:28])=[CH:7][N:6]=2)[CH2:9][CH2:10]1)=[O:15])([CH3:20])([CH3:19])[CH3:18]

Participants

7

Reactant 4

HCID 280Carbon DioxideHCID 313Hydrochloric AcidHCID 46739269tert-Butyl 4-(5-bromo-3-methylpyridin-2-yl)piperazine-1-carboxylateHCID 178418339Butyllithium2×

Product 1

HCID 68106369HCID 68106369, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Under an argon atmosphere, a solution of tert-butyl 4-(5-bromo-3-methylpyridin-2-yl)piperazine-1-carboxylate (400 mg) in THF (8 ml) was cooled to −78° C., and 1.63 M n-butyl lithium (0.9 ml) was added dropwise thereto, followed by stirring at the same temperature for 1 hour. Crushed dry ice was put into another flask, and THF (30 ml) was poured thereinto. The mixture to which n-BuLi had been added dropwise immediately before was added thereto, followed by stirring as it was for 1 hour. To the reaction mixture was added water and 1 M hydrochloric acid, and the pH of the aqueous layer was adjusted to around 5.0. The aqueous layer was extracted with EtOAc, the organic layer was separated, and then the aqueous layer was extracted with CHCl3 again. These organic layers were combined and dried over Na2SO4, and the solvent was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (CHCl3/MeOH) to obtain 6-[4-(tert-butoxycarbonyl)piperazine-1-yl]-5-methylnicotinic acid (169 mg).

Workup

  1. additionbefore was added
  2. stirringby stirring as it
  3. waitwas for 1 hour
  4. extractionThe aqueous layer was extracted with EtOAc
  5. customthe organic layer was separated
  6. extractionthe aqueous layer was extracted with CHCl3 again
  7. dry with materialdried over Na2SO4
  8. concentrationthe solvent was concentrated under reduced pressure
  9. customThe obtained residue was purified by silica gel column chromatography (CHCl3/MeOH)

Sources & evidence

ORD record
ord-cf393872df39406481d72e11fa776440
Source dataset
uspto-grants-2014_08
Patent number
US08802679B2

Reaction notes

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