Hydrochloric Acid → 2-(5-Bromo-6-(tert-butoxycarbonyl)pyridin-2-yl)-1,2,3,4-tetrahydroisoquinoline-8-carboxylic acid
Reaction equation
[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[C:11]([O:13]C)=[O:12])[CH2:4][CH2:3][NH:2]1.Cl.[Br:16][C:17]1[C:18]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[N:19][C:20](Cl)=[CH:21][CH:22]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C(=O)C.O>[Br:16][C:17]1[CH:22]=[CH:21][C:20]([N:2]2[CH2:3][CH2:4][C:5]3[C:10](=[C:9]([C:11]([OH:13])=[O:12])[CH:8]=[CH:7][CH:6]=3)[CH2:1]2)=[N:19][C:18]=1[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25]Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 120 °C
Procedure
A solution of methyl 1,2,3,4-tetrahydroisoquinoline-8-carboxylate, hydrochloric acid (13.6 g), tert-butyl 3-bromo-6-chloropicolinate (17.4 g) and cesium carbonate (39 g) were stirred together in N,N-dimethylacetamide (110 mL) and heated at 120° C. under nitrogen overnight. The reaction mixture was cooled, diluted with water and extracted with ethyl acetate. The organic layer was washed with brine and the combined aqueous layers were back-extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated. Silica gel chromatography using 20-100% ethyl acetate in hexanes provided the title compound.
Workup
- temperatureThe reaction mixture was cooled
- extractionextracted with ethyl acetate
- washThe organic layer was washed with brine
- extractionthe combined aqueous layers were back-extracted with ethyl acetate
- dry with materialThe combined organic layers were dried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-184a9ccc63f9497f9c50a9f96cebb4c8
- Source dataset
- uspto-grants-2016_01
- Patent number
- US09227963B2
Reaction notes
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