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

HRID 1960091Notes

Reaction equation

HRID 1960091 reaction equation
CC1C=CC(S(O[CH2:12][C:13]2[CH:17]=[C:16]([C:18]3[C:19]([N:24]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[N:20][CH:21]=[CH:22][CH:23]=3)[O:15][N:14]=2)(=O)=O)=CC=1.[N:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1[O:45][CH2:46][C:47]1[CH:52]=[CH:51][C:50](B(O)O)=[CH:49][CH:48]=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:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1[O:45][CH2:46][C:47]1[CH:52]=[CH:51][C:50]([CH2:12][C:13]2[CH:17]=[C:16]([C:18]3[C:19]([N:24]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[C:25]([O:27][C:28]([CH3:31])([CH3:29])[CH3:30])=[O:26])=[N:20][CH:21]=[CH:22][CH:23]=3)[O:15][N:14]=2)=[CH:49][CH:48]=1

Participants

10

Reactant 5

HCID 11776TriphenylphosphineHCID 62657Potassium Phosphate, TribasicHCID 44159845(4-((Pyridin-2-yloxy)methyl)phenyl)boronic acidHCID 58488959(5-{2-[Bis(tert-butoxycarbonyl)amino]pyridin-3-yl}isoxazol-3-yl)methyl 4-methylbenzenesulfonateHCID 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 (5-{2-[bis(tert-butoxycarbonyl)amino]pyridin-3-yl}isoxazol-3-yl)methyl 4-methylbenzenesulfonate (82 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, (5-{2-[bis(tert-butoxycarbonyl)amino]pyridin-3-yl}isoxazol-3-yl)methyl 4-methyl benzenesulfonate, and di-tert-butyl [3-(3-methylisoxazol-5-yl)pyridin-2-yl]imidodicarbonate (63 mg:molar ratio of 59:33:8), as a pale 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-6b624ff0ed14468ea664cc3aa68b2110
Source dataset
uspto-grants-2013_04
Patent number
US08410277B2

Reaction notes

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