6-Chloronicotinic acid → 6-(4-((Tert-butoxy)carbonyl)piperazin-1-yl)pyridine-3-carboxylic acid
Reaction equation
Cl[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][N:3]=1.[N:11]1([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.CCN(C(C)C)C(C)C>CN(C)C(=O)C>[C:20]([O:19][C:17]([N:11]1[CH2:16][CH2:15][N:14]([C:2]2[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][N:3]=2)[CH2:13][CH2:12]1)=[O:18])([CH3:23])([CH3:21])[CH3:22]Participants
Conditions
- Temperature
- 130 °C
Procedure
6-Chloronicotinic acid was dissolved in N,N-dimethylacetamide (10 ml), and tert-butyl piperazine-1-carboxylate (1.2 g) and DIPEA (1.6 g) were added thereto, followed by stirring at 130° C. for 3 days. The reaction mixture was concentrated under reduced pressure, and to the obtained residue was added a 1 M aqueous NaOH solution, followed by washing with CHCl3. The pH of the aqueous layer was adjusted to around 6 to 7 by the addition of 1 M hydrochloric acid, followed by extraction with CHCl3. The organic layer was 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)piperazin-1-yl]nicotinic acid (934 mg).
Workup
- concentrationThe reaction mixture was concentrated under reduced pressure
- additionto the obtained residue was added a 1 M aqueous NaOH solution
- washby washing with CHCl3
- additionThe pH of the aqueous layer was adjusted to around 6 to 7 by the addition of 1 M hydrochloric acid
- extractionfollowed by extraction with CHCl3
- dry with materialThe organic layer was dried over Na2SO4
- concentrationthe solvent was concentrated under reduced pressure
- customThe obtained residue was purified by silica gel column chromatography (CHCl3/MeOH)
Sources & evidence
- ORD record
- ord-24bca8e57e374188bc5c0eb60c0e8981
- Source dataset
- uspto-grants-2014_08
- Patent number
- US08802679B2
Reaction notes
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