Water → methyl 5-((2,2-dimethyltetrahydro-2H-pyran-4-yl)methoxy)-6-(2-fluoro-5-methoxyphenyl)nicotinate

HRID 709808Notes

Reaction equation

HRID 709808 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[C:19]([OH:20])=[CH:18][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][N:11]=1.Br[CH2:22][CH:23]1[CH2:28][CH2:27][O:26][C:25]([CH3:30])([CH3:29])[CH2:24]1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[CH3:29][C:25]1([CH3:30])[CH2:24][CH:23]([CH2:22][O:20][C:19]2[C:10]([C:3]3[CH:4]=[C:5]([O:8][CH3:9])[CH:6]=[CH:7][C:2]=3[F:1])=[N:11][CH:12]=[C:13]([CH:18]=2)[C:14]([O:16][CH3:17])=[O:15])[CH2:28][CH2:27][O:26]1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 576996994-(Bromomethyl)-2,2-dimethyloxaneHCID 117759971Methyl 6-(2-fluoro-5-methoxyphenyl)-5-hydroxynicotinate

Product 1

HCID 117760026methyl 5-((2,2-dimethyltetrahydro-2H-pyran-4-yl)methoxy)-6-(2-fluoro-5-methoxyphenyl)nicotinateYield 88.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl 6-(2-fluoro-5-methoxyphenyl)-5-hydroxynicotinate (739 mg) and 4-(bromomethyl)-2,2-dimethyltetrahydro-2H-pyran (828 mg) in DMF (20 mL) was added potassium carbonate (736 mg), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was poured into water (100 mL), and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/petroleum ether) to give the title compound (950 mg) as a colorless oil.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. dry with materialThe extract was dried over anhydrous sodium sulfate
  3. customthe solvent was evaporated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-24407a1bb0b84aafae52efeb242714df
Source dataset
uspto-grants-2015_11
Patent number
US09181186B2

Reaction notes

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