Toluene → HCID 86709385, compound

HRID 2172215Notes

Reaction equation

HRID 2172215 reaction equation
C1(C)C=CC=CC=1.Br[C:9]1[CH:14]=[CH:13][C:12]([O:15][CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][O:17]2)=[CH:11][N:10]=1.[F:22][C:23]([F:41])([F:40])[O:24][C:25]1[CH:39]=[CH:38][C:28]([O:29][CH2:30][CH2:31][CH:32]2[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)=[CH:27][CH:26]=1.CC(C)([O-])C.[Na+]>O>[O:17]1[CH2:18][CH2:19][CH2:20][CH2:21][CH:16]1[O:15][C:12]1[CH:13]=[CH:14][C:9]([N:35]2[CH2:36][CH2:37][CH:32]([CH2:31][CH2:30][O:29][C:28]3[CH:38]=[CH:39][C:25]([O:24][C:23]([F:22])([F:40])[F:41])=[CH:26][CH:27]=3)[CH2:33][CH2:34]2)=[N:10][CH:11]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 23676156Sodium t-butoxideHCID 70873620HCID 70873620, compoundHCID 866148912-Bromo-5-(2-tetrahydropyranyloxy)pyridine

Product 1

HCID 86709385HCID 86709385, compoundYield 95.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

Toluene (15 ml) was added to a mixture of 2-bromo-5-(tetrahydropyran-2-yloxy)pyridine (2.58 g, 10 mmol), 4-[2-(4-trifluoromethoxyphenoxy)ethyl]piperidine (3.18 g, 11 mmol) and sodium tert-butoxide (1.35 g, 14 mmol), and then the atmosphere was replaced with nitrogen. Bis(dibenzylideneacetone)palladium (Pd2(dba)3 complex) (0.23 g, 0.25 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthine (xantphos) (0.36 g, 0.63 mmol) were added to the mixture, and the reaction mixture was heated at 100° C. for 3 hours under a nitrogen atmosphere. After being cooled to room temperature, the reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with a saturated sodium chloride aqueous solution, dried over sodium sulfate, and concentrated. The result was purified by silica gel column chromatography (ethyl acetate:hexane=10:90→25:75) to afford the title compound as a pale brown powder (4.45 g, 95%).

Workup

  1. temperatureAfter being cooled to room temperature
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with a saturated sodium chloride aqueous solution
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe result was purified by silica gel column chromatography (ethyl acetate:hexane=10:90→25:75)

Sources & evidence

ORD record
ord-17fe152e6a4e4240a5cb391eaba9dabe
Source dataset
uspto-grants-2015_06
Patent number
US09051333B2

Reaction notes

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