2,5-Dibromopyridine → 5-Bromo-2-(3-(2-chloro-3,6-difluorophenyl)isoxazol-5-ylmethoxy)pyridine

HRID 2428195Notes

Reaction equation

HRID 2428195 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[Cl:9][C:10]1[C:15]([F:16])=[CH:14][CH:13]=[C:12]([F:17])[C:11]=1[C:18]1[CH:22]=[C:21]([CH2:23][OH:24])[O:20][N:19]=1.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([O:24][CH2:23][C:21]2[O:20][N:19]=[C:18]([C:11]3[C:12]([F:17])=[CH:13][CH:14]=[C:15]([F:16])[C:10]=3[Cl:9])[CH:22]=2)=[N:3][CH:4]=1

Participants

7

Reactant 3

HCID 693532,5-DibromopyridineHCID 23676156Sodium t-butoxideHCID 67148834HCID 67148834, compound

Product 1

HCID 671485775-Bromo-2-(3-(2-chloro-3,6-difluorophenyl)isoxazol-5-ylmethoxy)pyridineYield 65%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

2,5-Dibromopyridine (12.6 g, 53.0 mmol) and [3-(2-chloro-3,6-difluoro-phenyl)-isoxazol-5-yl]-methanol (10.0 g, 40.7 mmol) were dissolved in toluene (400 mL). tBuONa (5.87 g, 61.1 mmol), xantphos (1.42 g, 2.45 mmol) and Pd2(dba)3 (732 mg, 0.800 mmol) were added to the sol. The resulting mixture was refluxed overnight, and was allowed to cool down to rt. The mixture was filtered through Celite (washed with EtOAc), and was washed with aq. sat. NaHCO3 (1×) and brine (2×). The org. layer was dried over MgSO4, filtered, and concentrated under reduced pressure. Purification of the crude by FC (EtOAc/heptane 10:90) yielded the title compound (10.6 g, 65%). LC-MS: tR=1.10 min; ES+: 400.66.

Workup

  1. temperaturewas refluxed overnight
  2. filtrationThe mixture was filtered through Celite (washed with EtOAc)
  3. washwas washed with aq. sat. NaHCO3 (1×) and brine (2×)
  4. dry with materiallayer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification of the crude by FC (EtOAc/heptane 10:90)

Sources & evidence

ORD record
ord-36ba01bb74b544d8a00c62a100345932
Source dataset
uspto-grants-2011_06
Patent number
US07968720B2

Reaction notes

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