Potassium Phosphate, Tribasic → HCID 86664223, compound

HRID 1184484Notes

Reaction equation

HRID 1184484 reaction equation
P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH2:9]([B-](F)(F)F)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[K+].Cl[C:22]1[C:27]2[O:28][CH:29]([CH3:33])[C:30](=[O:32])[NH:31][C:26]=2[CH:25]=[C:24]([CH:34]=[O:35])[CH:23]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1>C1(C)C=CC=CC=1.O.CC(O)C>[CH2:9]([C:22]1[C:27]2[O:28][CH:29]([CH3:33])[C:30](=[O:32])[NH:31][C:26]=2[CH:25]=[C:24]([CH:34]=[O:35])[CH:23]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 23692459Potassium benzyltrifluoroboranuideHCID 866642218-Chloro-2-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbaldehyde

Product 1

HCID 86664223HCID 86664223, compoundYield 28.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
115 °C

Procedure

To a suspension of potassium phosphate, tribasic (0.564 g, 2.66 mmol), potassium benzyltrifluoroborate (0.263 g, 1.330 mmol), 8-chloro-2-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbaldehyde 15 (0.2 g, 0.886 mmol) in toluene (Ratio: 5.00, 20 mL) and water (Ratio: 1.000, 4.0 mL) was added PdOAc2 (0.015 g, 0.066 mmol) and dicyclohexyl(2′,6′-diisopropoxybiphenyl-2-yl)phosphine (0.062 g, 0.133 mmol) at 23° C. The reaction was stirred at 115° C. for 20 hr. The reaction mixture was poured into water (2 mL) and extracted with Et2O (3×5 mL). The organic layer was dried over Na2SO4, filtered, and the organic phase stripped to dryness via rotary evaporation. The resulting crude material was reconstituted in DCM (1.0 mL) and purified via medium pressure chromatography using a gradient eluant of 1-5% MeOH:DCM. The appropriate fractions were combined and solvent was removed via rotary evaporation. The late eluting fractions were dried in vacuo to provide a yellow solid. The yellow solid was re-suspended in IPA (1.0 mL), heated at reflux to furnish a solution, cooled to room temperature, filtered, rinsed with IPA, and dried in vacuo to provide the title compound as an off-white solid (0.0704 g, 0.250 mmol, 28.2% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.36 (d, J=6.82 Hz, 3H) 3.98 (s, 2H) 4.75-4.81 (m, 1H) 7.16-7.32 (m, 6H) 7.45 (d, J=2.02 Hz, 1H) 9.80 (s, 1H) 10.93 (s, 1H). ESI-MS: m/z 282.2 (M+H)+. mp=163.2-166.1° C.

Workup

  1. additionwas added
  2. customat 23° C
  3. extractionextracted with Et2O (3×5 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. customthe organic phase stripped to dryness via rotary evaporation
  7. custompurified via medium pressure chromatography
  8. customsolvent was removed via rotary evaporation
  9. washThe late eluting fractions
  10. customwere dried in vacuo
  11. customto provide a yellow solid
  12. temperatureheated
  13. temperatureat reflux
  14. customto furnish a solution
  15. temperaturecooled to room temperature
  16. filtrationfiltered
  17. washrinsed with IPA
  18. customdried in vacuo

Sources & evidence

ORD record
ord-70fc821f69d74a2dbf7b00581f7e2830
Source dataset
uspto-grants-2014_03
Patent number
US08669249B2

Reaction notes

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