Potassium Carbonate → HCID 86718603, compound

HRID 1480638Notes

Reaction equation

HRID 1480638 reaction equation
Br[C:2]1[C:11]2[O:10][CH2:9][N:8]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:7][C:6]=2[CH:5]=[C:4]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[CH:3]=1.[F:23][C:24]([F:35])([F:34])[C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][N:26]=1.C(=O)([O-])[O-].[K+].[K+]>C(COC)OC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:12]([N:8]1[CH2:7][C:6]2[CH:5]=[C:4]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[CH:3]=[C:2]([C:28]3[CH:27]=[N:26][C:25]([C:24]([F:35])([F:34])[F:23])=[CH:30][CH:29]=3)[C:11]=2[O:10][CH2:9]1)([CH3:15])([CH3:14])[CH3:13]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 251342782-(Trifluoromethyl)pyridine-5-boronic AcidHCID 86718604HCID 86718604, compound

Product 1

HCID 86718603HCID 86718603, compoundYield 37%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 8-bromo-3-(tert-butyl)-6-(4-fluorophenyl)-3,4-dihydro-2H-benzo[e][1,3]oxazine (2.0 g, 5.49 mmol), 2-(trifluoromethyl)pyridine-5-boronic acid [purchased from Frontier Scientific] (1.26 g, 6.59 mmol) and potassium carbonate (1.52 g, 10.98 mmol) in dimethoxyethane (15 mL) and water (5 mL) was purged with nitrogen for 20 minutes. Tetrakis(triphenylphosphine)palladium(0) (317.2 mg, 0.275 mmol) was added and the reaction mixture heated at 80° C. in a sealed vial for 17 hours. The cooled reaction mixture was partitioned between ethyl acetate (80 mL) and 1.0 M aqueous sodium hydroxide solution (80 mL), the organic phase separated, washed with water (80 mL) and saturated brine (80 mL), dried (MgSO4), filtered and concentrated under reduced pressure to give an orange syrup. The crude product was purified by chromatography on silica eluting with a solvent gradient of 0 to 8% methanol (containing 1% aqueous ammonium hydroxide) in dichloromethane to give 3-(tert-butyl)-6-(4-fluorophenyl)-8-(6-(trifluoromethyl)pyridin-3-yl)-3,4-dihydro-2H-benzo[e][1,3]oxazine (0.773 g, 37% yield) as a colorless syrup.

Workup

  1. customwas purged with nitrogen for 20 minutes
  2. customThe cooled reaction mixture
  3. customwas partitioned between ethyl acetate (80 mL) and 1.0 M aqueous sodium hydroxide solution (80 mL)
  4. customthe organic phase separated
  5. washwashed with water (80 mL) and saturated brine (80 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give an orange syrup
  10. customThe crude product was purified by chromatography on silica eluting with a solvent gradient of 0 to 8% methanol (containing 1% aqueous ammonium hydroxide) in dichloromethane

Sources & evidence

ORD record
ord-e8cdedbbbce74f3aaf68f1b7e9652024
Source dataset
uspto-grants-2016_08
Patent number
US09409893B2

Reaction notes

Loading…