Sodium hydride → Ethyl 3-cyclopropyl-3-(6-((5-(2-fluoro-5-methoxyphenyl)-6-neopentylpyridin-2-yl)methoxy)pyrimidin-4-yl)propanoate

HRID 709636Notes

Reaction equation

HRID 709636 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[CH:11]=[CH:12][C:13]([CH2:21][OH:22])=[N:14][C:15]=1[CH2:16][C:17]([CH3:20])([CH3:19])[CH3:18].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+]>C1COCC1.C(OCC)(=O)C.O>[CH:37]1([CH:30]([C:26]2[CH:25]=[C:24]([O:22][CH2:21][C:13]3[CH:12]=[CH:11][C:10]([C:3]4[CH:4]=[C:5]([O:8][CH3:9])[CH:6]=[CH:7][C:2]=4[F:1])=[C:15]([CH2:16][C:17]([CH3:19])([CH3:18])[CH3:20])[N:14]=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 3

HCID 24758Sodium hydrideHCID 117759814(5-(2-Fluoro-5-methoxyphenyl)-6-neopentylpyridin-2-yl)methanolHCID 117760030Ethyl 3-(6-chloropyrimidin-4-yl)-3-cyclopropylpropanoate

Product 1

HCID 117759970Ethyl 3-cyclopropyl-3-(6-((5-(2-fluoro-5-methoxyphenyl)-6-neopentylpyridin-2-yl)methoxy)pyrimidin-4-yl)propanoateYield 77.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (5-(2-fluoro-5-methoxyphenyl)-6-neopentylpyridin-2-yl)methanol (504 mg) and ethyl 3-(6-chloropyrimidin-4-yl)-3-cyclopropylpropanoate (465 mg) in THF (5.0 mL) was added 60% sodium hydride (86 mg) at 0° C., and the mixture was stirred at room temperature for 14 hr. The reaction mixture was diluted with ethyl acetate, and water was added at room temperature. 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, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (672 mg) as a pale-yellow oil.

Workup

  1. additionwas added at room temperature
  2. extractionThe reaction mixture was extracted with ethyl acetate
  3. washthe extract was washed with water and saturated brine
  4. dry with materialThe organic layer was dried over anhydrous magnesium 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-1939019c28aa4a50a7b1b317de0fb976
Source dataset
uspto-grants-2015_11
Patent number
US09181186B2

Reaction notes

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