Hydrochloric Acid → 3-Cyclopropyl-3-(6-((6-(2-fluoro-5-methoxyphenyl)-5-(3,3,3-trifluoropropoxy)pyridin-3-yl) methoxy)pyrimidin-4-yl)propanoic acid

HRID 709794Notes

Reaction equation

HRID 709794 reaction equation
[CH:1]1([CH:4]([C:11]2[CH:16]=[C:15]([O:17][CH2:18][C:19]3[CH:20]=[N:21][C:22]([C:32]4[CH:37]=[C:36]([O:38][CH3:39])[CH:35]=[CH:34][C:33]=4[F:40])=[C:23]([O:25][CH2:26][CH2:27][C:28]([F:31])([F:30])[F:29])[CH:24]=3)[N:14]=[CH:13][N:12]=2)[CH2:5][C:6]([O:8]CC)=[O:7])[CH2:3][CH2:2]1.[OH-].[Na+].Cl>CO>[CH:1]1([CH:4]([C:11]2[CH:16]=[C:15]([O:17][CH2:18][C:19]3[CH:20]=[N:21][C:22]([C:32]4[CH:37]=[C:36]([O:38][CH3:39])[CH:35]=[CH:34][C:33]=4[F:40])=[C:23]([O:25][CH2:26][CH2:27][C:28]([F:30])([F:29])[F:31])[CH:24]=3)[N:14]=[CH:13][N:12]=2)[CH2:5][C:6]([OH:8])=[O:7])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 117760120Ethyl 3-cyclopropyl-3-(6-((6-(2-fluoro-5-methoxyphenyl)-5-(3,3,3-trifluoropropoxy) pyridin-3-yl)methoxy)pyrimidin-4-yl)propanoate

Product 1

HCID 1177601213-Cyclopropyl-3-(6-((6-(2-fluoro-5-methoxyphenyl)-5-(3,3,3-trifluoropropoxy)pyridin-3-yl) methoxy)pyrimidin-4-yl)propanoic acidYield 63.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of ethyl 3-cyclopropyl-3-(6-((6-(2-fluoro-5-methoxyphenyl)-5-(3,3,3-trifluoropropoxy) pyridin-3-yl)methoxy)pyrimidin-4-yl)propanoate (53 mg) in methanol (1.0 mL) was added 2N aqueous sodium hydroxide (235 μL) solution at room temperature, and the mixture was stirred for 20 hr. The reaction mixture was cooled to 0° C., neutralized with 1N hydrochloric acid and extracted with ethyl acetate. The extract was washed with saturated brine. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by preparative HPLC (C18, mobile phase: water/acetonitrile (10 mM NH4HCO3-containing system)), and the obtained fraction was evaporated under reduced pressure to give the title compound (32 mg) as a colorless oil.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by preparative HPLC (C18, mobile phase: water/acetonitrile (10 mM NH4HCO3-containing system))
  6. customthe obtained fraction was evaporated under reduced pressure

Sources & evidence

ORD record
ord-6e632cfbc5874e39a23e225fc2580cd0
Source dataset
uspto-grants-2015_11
Patent number
US09181186B2

Reaction notes

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