Water → methyl 6-chloro-5-((tetrahydro-2H-pyran-2-yl)oxy)nicotinate

HRID 709786Notes

Reaction equation

HRID 709786 reaction equation
[Cl:1][C:2]1[C:11]([OH:12])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1.[O:13]1[CH:18]=[CH:17][CH2:16][CH2:15][CH2:14]1.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1.O>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:11]([O:12][CH:14]2[CH2:15][CH2:16][CH2:17][CH2:18][O:13]2)=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 80803,4-dihydro-2H-pyranHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 46941479Methyl 6-chloro-5-hydroxynicotinate

Product 1

HCID 117759840methyl 6-chloro-5-((tetrahydro-2H-pyran-2-yl)oxy)nicotinate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

Under a nitrogen atmosphere, to a solution of methyl 6-chloro-5-hydroxynicotinate (703 mg) in toluene (15 mL) were added 3,4-dihydro-2H-pyran (685 μL) and pyridinium p-toluenesulfonate (94 mg), and the mixture was stirred at room temperature for 2 hr and further at 60° C. for 1.5 hr. The reaction mixture was poured into water at room temperature, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (546 mg) as a white solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-508645f2e1cd4c9fbd080a8d69ac5fdf
Source dataset
uspto-grants-2015_11
Patent number
US09181186B2

Reaction notes

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