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

HRID 709612Notes

Reaction equation

HRID 709612 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:5]=1[C:12]1[CH:13]=[CH:14][C:15]([CH2:23][OH:24])=[N:16][C:17]=1[O:18][CH2:19][CH:20]([CH3:22])[CH3:21].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.Cl>C1COCC1>[CH:39]1([CH:32]([C:28]2[CH:27]=[C:26]([O:24][CH2:23][C:15]3[CH:14]=[CH:13][C:12]([C:5]4[CH:6]=[C:7]([O:10][CH3:11])[CH:8]=[CH:9][C:4]=4[F:3])=[C:17]([O:18][CH2:19][CH:20]([CH3:21])[CH3:22])[N:16]=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 117760030Ethyl 3-(6-chloropyrimidin-4-yl)-3-cyclopropylpropanoateHCID 117760235(5-(2-Fluoro-5-methoxyphenyl)-6-isobutoxypyridin-2-yl)methanol

Product 1

HCID 117760197Ethyl 3-cyclopropyl-3-(6-((5-(2-fluoro-5-methoxyphenyl)-6-isobutoxypyridin-2-yl)methoxy)pyrimidin-4-yl)propanoateYield 57.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

60% Sodium hydride (34 mg) was added to a solution of (5-(2-fluoro-5-methoxyphenyl)-6-isobutoxypyridin-2-yl)methanol (200 mg) and ethyl 3-(6-chloropyrimidin-4-yl)-3-cyclopropylpropanoate (167 mg) in THF (6.0 mL) at 0° C., and the mixture was stirred at room temperature for 30 min and at 50° C. for 4 hr. 1N Hydrochloric acid was added to the reaction mixture at 0° C., and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) and silica gel column chromatography (NH, ethyl acetate/hexane) to give the title compound (198 mg) as a colorless oil.

Workup

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

Sources & evidence

ORD record
ord-f829f08a8ade48309bbf282431246295
Source dataset
uspto-grants-2015_11
Patent number
US09181186B2

Reaction notes

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