Potassium Phosphate, Tribasic → 2-Methyl-3-oxo-8-phenyl-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbaldehyde

HRID 1184479Notes

Reaction equation

HRID 1184479 reaction equation
P([O-])([O-])([O-])=O.[K+].[K+].[K+].[C:9]1([B-](F)(F)F)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[K+].Cl[C:21]1[C:26]2[O:27][CH:28]([CH3:32])[C:29](=[O:31])[NH:30][C:25]=2[CH:24]=[C:23]([CH:33]=[O:34])[CH:22]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1>C1(C)C=CC=CC=1.O>[CH3:32][CH:28]1[O:27][C:26]2[C:21]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)=[CH:22][C:23]([CH:33]=[O:34])=[CH:24][C:25]=2[NH:30][C:29]1=[O:31]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 23675248Potassium phenyltrifluoroborateHCID 866642218-Chloro-2-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbaldehyde

Product 1

HCID 866642222-Methyl-3-oxo-8-phenyl-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbaldehydeYield 19.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
115 °C

Procedure

To a solution of potassium phosphate, tribasic (0.564 g, 2.66 mmol), potassium phenyltrifluoroborate (0.245 g, 1.330 mmol), and 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: 4.00, 16 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 42 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 purified via medium pressure chromatography using a gradient eluant of CH2Cl2/MeOH. The appropriate fractions were combined and concentrated via rotary evaporation. The impure material was reconstituted in DMSO (1.0 mL) and purified via preparative mass trigger LCMS using a gradient eluant of 45-70% ACN:0.05% TFA (aq). The early fractions were combined and the solvent was removed via rotary evaporation. The purified product was dried in vacuo to provide the title compound as an off-white solid (0.0459 g, 0.172 mmol, 19.37% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.44 (d, J=6.82 Hz, 3H) 4.85-4.92 (m, 1H) 7.38-7.43 (m, 2H) 7.46-7.51 (m, 2H) 7.57-7.62 (m, 2H) 7.64 (d, J=2.02 Hz, 1H) 9.91 (s, 1H) 11.04 (s, 1H). ESI-MS: m/z 268.1 (M+H)+.

Workup

  1. customat 23° C
  2. extractionextracted with Et2O (3×5 mL)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. customthe organic phase stripped to dryness via rotary evaporation
  6. customThe resulting crude material was purified via medium pressure chromatography
  7. concentrationconcentrated via rotary evaporation
  8. custompurified via preparative mass trigger LCMS
  9. customthe solvent was removed via rotary evaporation
  10. customThe purified product was dried in vacuo

Sources & evidence

ORD record
ord-caba84948af24a6b826909f8adf1b6de
Source dataset
uspto-grants-2014_03
Patent number
US08669249B2

Reaction notes

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