Water → Ethyl 3-cyclopropyl-3-(6-((6-(2-fluoro-5-methoxyphenyl)-5-(3,3,3-trifluoropropoxy) pyridin-3-yl)methoxy)pyrimidin-4-yl)propanoate

HRID 709793Notes

Reaction equation

HRID 709793 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:26]4[CH:31]=[C:30]([O:32][CH3:33])[CH:29]=[CH:28][C:27]=4[F:34])=[C:23]([OH:25])[CH:24]=3)[N:14]=[CH:13][N:12]=2)[CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH2:3][CH2:2]1.[F:35][C:36]([F:41])([F:40])[CH2:37][CH2:38]O.C(C=P(CCCC)(CCCC)CCCC)#N.O>C1(C)C=CC=CC=1>[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:26]4[CH:31]=[C:30]([O:32][CH3:33])[CH:29]=[CH:28][C:27]=4[F:34])=[C:23]([O:25][CH2:38][CH2:37][C:36]([F:41])([F:40])[F:35])[CH:24]=3)[N:14]=[CH:13][N:12]=2)[CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 962WaterHCID 1375123,3,3-Trifluoro-1-propanolHCID 4622928CyanomethylenetributylphosphoraneHCID 117759845Ethyl 3-cyclopropyl-3-(6-((6-(2-fluoro-5-methoxyphenyl)-5-hydroxypyridin-3-yl)methoxy)pyrimidin-4-yl)propanoate

Product 1

HCID 117760120Ethyl 3-cyclopropyl-3-(6-((6-(2-fluoro-5-methoxyphenyl)-5-(3,3,3-trifluoropropoxy) pyridin-3-yl)methoxy)pyrimidin-4-yl)propanoate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Under a nitrogen atmosphere, to a solution of ethyl 3-cyclopropyl-3-(6-((6-(2-fluoro-5-methoxyphenyl)-5-hydroxypyridin-3-yl)methoxy)pyrimidin-4-yl)propanoate (57 mg) in toluene (1.2 mL) were added 3,3,3-trifluoro-1-propanol (21 μL) and cyanomethylenetributylphosphorane (64 uL), and the mixture was stirred at 100° C. for 4 hr. After allowing to cool to room temperature, the reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. 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) to give the title compound (53 mg) as a pale-yellow amorphous solid.

Workup

  1. temperatureto cool to room temperature
  2. extractionthe 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-fa95ecff473e45c0b3baf9be1d8287e3
Source dataset
uspto-grants-2015_11
Patent number
US09181186B2

Reaction notes

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