Dimethylformamide → 3-[5-Fluoro-3-(tetrahydro-pyran-4-YL)-pyridin-2-yloxy]-cyclobutanecarboxylic acid methoxy-methyl-amide
Reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)[C:5]([O:8][CH:9]2[CH2:12][CH:11]([C:13](O)=[O:14])[CH2:10]2)=[N:6][CH:7]=1.CN([CH:25]=[O:26])C.[CH2:27]([N:29](CC)CC)C>O.CCOC(C)=O>[CH3:25][O:26][N:29]([CH3:27])[C:13]([CH:11]1[CH2:10][CH:9]([O:8][C:5]2[C:4]([CH:16]3[CH2:17][CH2:18][O:19][CH2:20][CH2:21]3)=[CH:3][C:2]([F:1])=[CH:7][N:6]=2)[CH2:12]1)=[O:14]Participants
6
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Procedure
To a solution of 3-[5-fluoro-3-(tetrahydro-pyran-4-yl)-pyridin-2-yloxy]-cyclobutanecarboxylic acid (1.5 g, 4.68 mmol) was added DMF (20 mL), triethylamine (1 mL, 7.02 mmol), and 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (2.24 g, 5.90 mmol). The reaction mixture was stirred at RT for 1d. Then it was diluted with water and EtOAc. The organic layer was separated and the aqueous phase was extracted with EtOAc (2×10 mL). All the organic layers were combined and washed with brine (1×10 mL), dried over MgSO4, filtered, and concentrated to get a crude, which was purified by flash column chromatography on silica gel (30% to 70% EtOAc in hexanes) to give the product (2.2 g) as yellow oil.
Workup
- customThe organic layer was separated
- extractionthe aqueous phase was extracted with EtOAc (2×10 mL)
- washwashed with brine (1×10 mL)
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated
- customto get a crude, which
- customwas purified by flash column chromatography on silica gel (30% to 70% EtOAc in hexanes)
Sources & evidence
- ORD record
- ord-142f47cf0368442e91b6656311468350
- Source dataset
- uspto-grants-2015_02
- Patent number
- US08952037B2
Reaction notes
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