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

HRID 1930777Notes

Reaction equation

HRID 1930777 reaction equation
[C:1]([O:5][C:6]([N:8]([C:16]1[C:21]([C:22]2[O:26][N:25]=[C:24]([CH2:27]Cl)[CH:23]=2)=[CH:20][CH:19]=[CH:18][N:17]=1)[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[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.C(=O)([O-])[O-].[Cs+].[Cs+].[Cl-].[Na+]>[Cu]I.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(OCC)(=O)C.COCCOC>[C:1]([O:5][C:6]([N:8]([C:16]1[C:21]([C:22]2[O:26][N:25]=[C:24]([CH2:27][C:40]3[CH:39]=[CH:38][C:37]([CH2:36][O:35][C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][N:29]=4)=[CH:42][CH:41]=3)[CH:23]=2)=[CH:20][CH:19]=[CH:18][N:17]=1)[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 5234Sodium ChlorideHCID 10796Cesium carbonateHCID 44159845(4-((Pyridin-2-yloxy)methyl)phenyl)boronic acid2×HCID 57867420Di-tert-butyl {3-[3-(chloromethyl)isoxazol-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)imidodicarbonateYield 77.4%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Under nitrogen atmosphere, to a mixture of di-tert-butyl{3-[3-(chloromethyl)isoxazol-5-yl]pyridin-2-yl}imidodicarbonate (164 mg, 0.40 mmol), {4-[(pyridin-2-yloxy)methyl]phenyl}boronic acid (138 mg, 0.60 mmol), cesium carbonate (391 mg, 1.20 mmol), copper(I) iodide (3.9 mg, 5 mol %) and 1,2-dimethoxyethane (2.0 mL) was added [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) dichloromethane complex (16.4 mg, 5 mol %), which was stirred at 80° C. for 1.5 hours. {4-[(Pyridin-2-yloxy)methyl]phenyl}boronic acid (46 mg, 0.20 mmol) was added thereto and the solution was further stirred for 4.5 hours. After cooling, ethyl acetate and 5% sodium chloride solution were added thereto, insoluble matter was filtered out, then, the filtrate was transferred to a separatory funnel and separated. After the organic layer was washed with 5% sodium chloride water and dried over anhydrous magnesium sulfate, the solvent was evaporated under a reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (173 mg) as a pale yellow oily product.

Workup

  1. stirringthe solution was further stirred for 4.5 hours
  2. temperatureAfter cooling
  3. filtrationinsoluble matter was filtered out
  4. customthe filtrate was transferred to a separatory funnel
  5. customseparated
  6. washAfter the organic layer was washed with 5% sodium chloride water
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customthe solvent was evaporated under a reduced pressure
  9. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-9b50bdc61027436b8fb8a8b9d5689725
Source dataset
uspto-grants-2012_05
Patent number
US08188119B2

Reaction notes

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