Methanol → HCID 86657651, compound
Reaction equation
Br[C:2]1[CH:3]=[C:4]([C:15]([F:18])([F:17])[F:16])[C:5]([O:8][C@@H:9]([CH3:14])[C:10]([F:13])([F:12])[F:11])=[N:6][CH:7]=1.[CH:19]1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[OH2:48].[CH3:49][OH:50]>CS(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:16][C:15]([F:18])([F:17])[C:4]1[C:5]([O:8][C@@H:9]([CH3:14])[C:10]([F:13])([F:12])[F:11])=[N:6][CH:7]=[C:2]([CH:3]=1)[C:49]([O:50][CH3:19])=[O:48]Participants
Conditions
- Temperature
- 70 °C
Procedure
5-Bromo-3-(trifluoromethyl)-2-{[(2S)-1,1,1-trifluoropropan-2-yl]oxy}pyridine (500 mg) was dissolved in a mixed vehicle of DMSO (5 mL) and MeOH (5 mL). Then, TEA (0.42 mL) was added thereto at 25° C., and then Pd(OAc)2(17 mg) and DPPP (60 mg) were added thereto at 25° C., followed by stirring at 70° C. for 15 hours under a CO atmosphere. To the reaction solution was added water (30 mL), followed by extraction with EtOAc (20 mL) three times. The organic layer was washed with brine, dried over MgSO4, and then filtered, and the filtrate was concentrated. The residue was purified by silica gel column chromatography (automatic purification device, developing solution; hexane:EtOAc=100:0 to 80:20) to obtain methyl 5-(trifluoromethyl)-6-{[(2S)-1,1,1-trifluoropropan-2-yl]oxy}nicotinate (403 mg) as a yellow solid.
Workup
- customat 25° C.
- extractionfollowed by extraction with EtOAc (20 mL) three times
- washThe organic layer was washed with brine
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationthe filtrate was concentrated
- customThe residue was purified by silica gel column chromatography (automatic purification device, developing solution; hexane:EtOAc=100:0 to 80:20)
Sources & evidence
- ORD record
- ord-8862875fb42a420ab5544d1042070585
- Source dataset
- uspto-grants-2012_06
- Patent number
- US08193378B2
Reaction notes
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