Water → HCID 117759869, compound

HRID 1049549Notes

Reaction equation

HRID 1049549 reaction equation
[CH:1]1([CH:4]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][O:18][C:19]3[CH:20]=[N:21][C:22](OS(C(F)(F)F)(=O)=O)=[C:23]([CH2:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH:24]=3)[CH:12]=2)[CH2:5][C:6]([O:8]CC)=[O:7])[CH2:3][CH2:2]1.[F:38][C:39]([F:51])([F:50])[O:40][C:41]1[CH:46]=[CH:45][C:44](B(O)O)=[CH:43][CH:42]=1.C(=O)([O-])[O-].[Na+].[Na+].O>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C>[CH:1]1([CH:4]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][O:18][C:19]3[CH:20]=[N:21][C:22]([C:44]4[CH:43]=[CH:42][C:41]([O:40][C:39]([F:38])([F:50])[F:51])=[CH:46][CH:45]=4)=[C:23]([CH2:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH:24]=3)[CH:12]=2)[CH2:5][C:6]([OH:8])=[O:7])[CH2:2][CH2:3]1

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27343864-(Trifluoromethoxy)phenylboronic acidHCID 117760141HCID 117760141, compound

Product 1

HCID 117759869HCID 117759869, compoundYield 23.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of ethyl 3-cyclopropyl-3-(3-(((5-neopentyl-6-(((trifluoromethyl)sulfonyl)oxy)pyridin-3-yl)oxy)methyl)phenyl)propanoate (65.2 mg) in toluene (1.5 mL) were added (4-(trifluoromethoxy)phenyl)boronic acid (24.7 mg), 2M aqueous sodium carbonate solution (720 μL), and tetrakis(triphenylphosphine)palladium(0) (13.8 mg), and the mixture was heated in a microwave synthesizer (Anton Parr, Synthos3000) at 100° C. for 90 min. Water (1 mL) and ethyl acetate (3 mL) were added to the reaction solution and the mixture was stirred. The organic layer was passed through a phase separation filter, and the solvent was evaporated by an air blowing apparatus. The residue was purified by HPLC (column: YMC Triart C18, mobile phase: acetonitrile/10 mM aqueous ammonium hydrogen carbonate solution) and the solvent was evaporated by an air blowing apparatus. To the residue were added ethanol (1 mL) and 2M aqueous lithium hydroxide solution (180 μL), and the mixture was stirred at 60° C. for 1 hr. 1M Hydrochloric acid (360 μL) was added and the obtained solution was purified by HPLC (column: YMC Triart C18, mobile phase: acetonitrile/10 mM aqueous ammonium hydrogen carbonate solution), and the solvent was evaporated by an air blowing apparatus to give the title compound (14.9 mg).

Workup

  1. customThe organic layer was passed through a phase separation
  2. filtrationfilter
  3. customthe solvent was evaporated by an air
  4. customThe residue was purified by HPLC (column: YMC Triart C18, mobile phase: acetonitrile/10 mM aqueous ammonium hydrogen carbonate solution)
  5. customthe solvent was evaporated by an air
  6. additionTo the residue were added ethanol (1 mL) and 2M aqueous lithium hydroxide solution (180 μL)
  7. stirringthe mixture was stirred at 60° C. for 1 hr
  8. addition1M Hydrochloric acid (360 μL) was added
  9. customthe obtained solution was purified by HPLC (column: YMC Triart C18, mobile phase: acetonitrile/10 mM aqueous ammonium hydrogen carbonate solution)
  10. customthe solvent was evaporated by an air

Sources & evidence

ORD record
ord-7f5c92e33fb745a296dfcc1ee84e3750
Source dataset
uspto-grants-2016_07
Patent number
US09382188B2

Reaction notes

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