Water → HCID 69673041, compound

HRID 1426320Notes

Reaction equation

HRID 1426320 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([C:12]([OH:14])=[O:13])[CH:3]=1.[CH2:15](N(CC)CC)[CH3:16].O.[OH-].[Na+]>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>[F:9][C:8]([F:11])([F:10])[C:6]1[N:5]=[C:4]([C:12]([OH:14])=[O:13])[CH:3]=[C:2]([CH:15]=[CH2:16])[CH:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 573690934-Bromo-6-(trifluoromethyl)pyridine-2-carboxylic acid

Product 1

HCID 69673041HCID 69673041, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-bromo-6-(trifluoromethyl)pyridine-2-carboxylic acid (0.50 g, 1.8 mmol, Anichem), (2-Ethenyl)tri-n-butyltin (919 μL, 3.14 mmol, Aldrich) and tetrakis(triphenylphosphine)palladium(0) (428 mg, 0.370 mmol, Strem) in toluene (4.2 mL) was degassed by a stream of nitrogen through the solution for 15 minutes. Triethylamine (774 μL, 5.56 mmol) was added and the mixture was heated to 80° C. for 2 hours. After cooling to ambient temperature, water and 1N NaOH were added and the product was extracted with four portions of ethyl acetate. The aqueous layer was then treated with 1N HCl to achieve a pH between 4 and 5, and was extracted with six portions of 10% isopropanol in chloroform. The combined organic extracts were dried over sodium sulfate, filtered and concentrated to afford crude product, which was used without further purification in Step B. H NMR (300 MHz, CDCl3) δ 8.40 (d, J=1.3 Hz, 1H), 7.88 (d, J=1.5 Hz, 1H), 6.82 (dd, J=17.6, 10.9 Hz, 1H), 6.23 (d, J=17.4 Hz, 1H), 5.78 (d, J=10.9 Hz, 1H); LCMS (M+H)+: 218.1.

Workup

  1. customwas degassed by a stream of nitrogen through the solution for 15 minutes
  2. temperatureAfter cooling to ambient temperature
  3. extractionthe product was extracted with four portions of ethyl acetate
  4. additionThe aqueous layer was then treated with 1N HCl
  5. extractionwas extracted with six portions of 10% isopropanol in chloroform
  6. dry with materialThe combined organic extracts were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto afford crude product, which
  10. customwas used without further purification in Step B

Sources & evidence

ORD record
ord-120b6d2e6ab04b4c8b22f6d8b7f4c213
Source dataset
uspto-grants-2015_01
Patent number
US08933085B2

Reaction notes

Loading…