Triphenylphosphine → Di-tert-butyl (3-(3-(4-((pyridin-2-yloxy)methyl)benzyl)isoxazol-5-yl)pyridin-2-yl)imidodicarbonate

HRID 1960090Notes

Reaction equation

HRID 1960090 reaction equation
Br[CH2:2][C:3]1[CH:7]=[C:6]([C:8]2[C:9]([N:14]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[N:10][CH:11]=[CH:12][CH:13]=2)[O:5][N:4]=1.[N:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[O:35][CH2:36][C:37]1[CH:42]=[CH:41][C:40](B(O)O)=[CH:39][CH:38]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC1C=C(C2C(N(C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)=NC=CC=2)ON=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C(OCC)(=O)C.C1(C)C=CC=CC=1>[N:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[O:35][CH2:36][C:37]1[CH:38]=[CH:39][C:40]([CH2:2][C:3]2[CH:7]=[C:6]([C:8]3[C:9]([N:14]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[N:10][CH:11]=[CH:12][CH:13]=3)[O:5][N:4]=2)=[CH:41][CH:42]=1

Participants

10

Reactant 5

HCID 11776TriphenylphosphineHCID 62657Potassium Phosphate, TribasicHCID 44159845(4-((Pyridin-2-yloxy)methyl)phenyl)boronic acidHCID 57867418Di-tert-butyl{3-[3-(bromomethyl)isoxazol-5-yl]pyridin-2-yl}imidodicarbonate2×HCID 67446064Di-tert-butyl [3-(3-methylisoxazol-5-yl)pyridin-2-yl]imidodicarbonate

Product 1

HCID 25114167Di-tert-butyl (3-(3-(4-((pyridin-2-yloxy)methyl)benzyl)isoxazol-5-yl)pyridin-2-yl)imidodicarbonate

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

Under a nitrogen atmosphere, to a mixture of di-tert-butyl {3-[3-(bromomethyl)isoxazol-5-yl]pyridin-2-yl}imidodicarbonate (68 mg, 0.15 mmol), {4-[(pyridin-2-yloxy)methyl]phenyl}boronic acid (34 mg, 0.15 mmol), potassium phosphate (35 mg, 0.17 mmol), triphenylphosphine (7.9 mg, 0.03 mmol), and toluene (1.0 mL) was added palladium acetate (1.7 mg, 5 mol %), which was stirred for 16 hours at 90° C. After cooling, ethyl acetate and water were added thereto, and the mixture was transferred to a separatory funnel and separated. The organic layer was washed with saturated sodium chloride solution and then dried over anhydrous magnesium sulfate, the solvent was evaporated under a reduced pressure. The residue was purified by silica gel column chromatography, so as to obtain a mixture of the titled compound, di-tert-butyl {3-[3-(bromomethyl)isoxazol-5-yl]pyridin-2-yl}imidodicarbonate, and di-tert-butyl [3-(3-methylisoxazol-5-yl)pyridin-2-yl}imidodicarbonate (54 mg:molar ratio of 53:36:11), as a yellow oil.

Workup

  1. temperatureAfter cooling
  2. customthe mixture was transferred to a separatory funnel
  3. customseparated
  4. washThe organic layer was washed with saturated sodium chloride solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated under a reduced pressure
  7. customThe residue was purified by silica gel column chromatography
  8. customso as to obtain

Sources & evidence

ORD record
ord-d744e4ee89824457a1dba04b32f8dc2a
Source dataset
uspto-grants-2013_04
Patent number
US08410277B2

Reaction notes

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