Hydrochloric Acid → ethyl 3-cyclopropyl-3-(6-((6-(2-fluoro-5-methoxyphenyl)-5-((tetrahydro-2H-pyran-2-yl)oxy)pyridin-3-yl)methoxy)pyrimidin-4-yl)propanoate

HRID 709789Notes

Reaction equation

HRID 709789 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[N:15]=[CH:14][C:13]([CH2:16][OH:17])=[CH:12][C:11]=1[O:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1.Cl[C:26]1[N:31]=[CH:30][N:29]=[C:28]([CH:32]([CH:39]2[CH2:41][CH2:40]2)[CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH:27]=1.[H-].[Na+].Cl>C1COCC1>[CH:39]1([CH:32]([C:28]2[CH:27]=[C:26]([O:17][CH2:16][C:13]3[CH:14]=[N:15][C:10]([C:3]4[CH:4]=[C:5]([O:8][CH3:9])[CH:6]=[CH:7][C:2]=4[F:1])=[C:11]([O:18][CH:19]4[CH2:24][CH2:23][CH2:22][CH2:21][O:20]4)[CH:12]=3)[N:31]=[CH:30][N:29]=2)[CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH2:41][CH2:40]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 117759989(6-(2-fluoro-5-methoxyphenyl)-5-((tetrahydro-2H-pyran-2-yl)oxy)pyridin-3-yl)methanolHCID 117760030Ethyl 3-(6-chloropyrimidin-4-yl)-3-cyclopropylpropanoate

Product 1

HCID 117760012ethyl 3-cyclopropyl-3-(6-((6-(2-fluoro-5-methoxyphenyl)-5-((tetrahydro-2H-pyran-2-yl)oxy)pyridin-3-yl)methoxy)pyrimidin-4-yl)propanoateYield 52.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Under a nitrogen atmosphere, to a solution of (6-(2-fluoro-5-methoxyphenyl)-5-((tetrahydro-2H-pyran-2-yl)oxy)pyridin-3-yl)methanol (189 mg) and ethyl 3-(6-chloropyrimidin-4-yl)-3-cyclopropylpropanoate (174 mg) in THF (2.8 mL) was added 60% sodium hydride (25 mg) at 0° C., and the mixture was stirred at room temperature for 2 hr. The reaction mixture was cooled to 0° C., and neutralized with 1N hydrochloric acid. The reaction mixture was extracted with ethyl acetate, and 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 and then methanol/ethyl acetate) to give the title compound (164 mg) as a colorless oil.

Workup

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. extractionThe reaction mixture was extracted with ethyl acetate
  3. washthe extract was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane

Sources & evidence

ORD record
ord-f71d47b7067045bab9f2c678142fe337
Source dataset
uspto-grants-2015_11
Patent number
US09181186B2

Reaction notes

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