Hydrochloric Acid → Ethyl 3-cyclopropyl-3-(6-((6-(2-fluoro-5-methoxyphenyl)-5-isobutoxypyridin-3-yl)methoxy)pyrimidin-4-yl)propanoate

HRID 709766Notes

Reaction equation

HRID 709766 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][CH2:19][CH:20]([CH3:22])[CH3:21].Cl[C:24]1[N:29]=[CH:28][N:27]=[C:26]([CH:30]([CH:37]2[CH2:39][CH2:38]2)[CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:25]=1.[H-].[Na+].Cl.C(=O)([O-])O.[Na+]>C1COCC1>[CH:37]1([CH:30]([C:26]2[CH:25]=[C:24]([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][CH2:19][CH:20]([CH3:22])[CH3:21])[CH:12]=3)[N:29]=[CH:28][N:27]=2)[CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH2:39][CH2:38]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 117760030Ethyl 3-(6-chloropyrimidin-4-yl)-3-cyclopropylpropanoateHCID 117760274(6-(2-Fluoro-5-methoxyphenyl)-5-isobutoxypyridin-3-yl)methanol

Product 1

HCID 117759893Ethyl 3-cyclopropyl-3-(6-((6-(2-fluoro-5-methoxyphenyl)-5-isobutoxypyridin-3-yl)methoxy)pyrimidin-4-yl)propanoateYield 88.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Under an argon atmosphere, to a solution of (6-(2-fluoro-5-methoxyphenyl)-5-isobutoxypyridin-3-yl)methanol (587 mg) and ethyl 3-(6-chloropyrimidin-4-yl)-3-cyclopropylpropanoate (587 mg) in THF (9.6 mL) was added 60% sodium hydride (100 mg) at 0° C., and the mixture was stirred at room temperature for 4 hr. 1N Hydrochloric acid was added to the reaction mixture at 0° C., and the mixture was neutralized with saturated aqueous sodium hydrogen carbonate solution. The reaction mixture was extracted with ethyl acetate, and the extract was washed with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (890 mg) as a colorless oil.

Workup

  1. extractionThe reaction mixture was extracted with ethyl acetate
  2. washthe extract was washed with water and saturated brine
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customthe obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-d5176756280f40e6a7efc7b14fd17d4e
Source dataset
uspto-grants-2015_11
Patent number
US09181186B2

Reaction notes

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