Heptane → 5-(4-Fluorophenyl)-6-cyclopropylmethoxy-nicotinic acid
Reaction equation
Br[C:2]1[C:3]([O:11][CH2:12][CH:13]2[CH2:15][CH2:14]2)=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].[F:16][C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=1.C(=O)([O-])[O-].[Na+].[Na+].CCCCCCC>C1(C)C=CC=CC=1.CN(C)C=O>[CH:13]1([CH2:12][O:11][C:3]2[C:2]([C:20]3[CH:21]=[CH:22][C:17]([F:16])=[CH:18][CH:19]=3)=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[CH:5][N:4]=2)[CH2:15][CH2:14]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 90 °C
Procedure
5-Bromo-6-cyclopropylmethoxy-nicotinic acid (2.28 g, 8 mmol) was dissolved in a mixture of toluene (40 mL) and dimethylformamide (4 mL). To this solution was added [4-fluoro-phenyl]-boronic acid (1.2 g, 8 mmol), [1,1′-bis(diphenylphosphino)-ferrocene]-dichloropalladium(II) dichloro-methane complex (307 mg), and 2 N sodium carbonate solution (33 mL). The whole mixture was heated with stirring at 90° C. for 4 h, cooled to room temperature and filtered. Phases were separated; the organic phase was discarded and the water phase was acidified with 1 N hydrochloric acid (pH 2) and extracted with ethylacetate. Etylacetate phases were pooled, dried with Na2SO4 and filtered over a small silica gel pad (20 g). The solvent was removed to yield a solid which was stirred with heptane (200 mL), filtered, washed with heptane and dried to yield 1.77 g of the title compound as beige solid, MS (ISP) 286.0 (M−H)−.
Workup
- temperatureThe whole mixture was heated
- temperaturecooled to room temperature
- filtrationfiltered
- customPhases were separated
- extractionextracted with ethylacetate
- dry with materialdried with Na2SO4
- filtrationfiltered over a small silica gel pad (20 g)
- customThe solvent was removed
- customto yield a solid which
- filtrationfiltered
- washwashed with heptane
- customdried
Sources & evidence
- ORD record
- ord-f598edf7a41345299a0b924ae470521d
- Source dataset
- uspto-grants-2007_06
- Patent number
- US07229999B2
Reaction notes
Loading…