Cesium carbonate → tert-Butyl 4-(2-oxo-7-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)benzylcarbamate

HRID 1509321Notes

Reaction equation

HRID 1509321 reaction equation
Br[C:2]1[C:3]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:4][C:5]2[N:10]([CH2:11][C:12]([F:15])([F:14])[F:13])[C:9](=[O:16])[CH2:8][O:7][C:6]=2[N:17]=1.CC1(C)C(C)(C)OB([C:32]2[CH:46]=[CH:45][C:35]([CH2:36][NH:37][C:38](=[O:44])[O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[CH:34][CH:33]=2)O1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O>[O:16]=[C:9]1[CH2:8][O:7][C:6]2[N:17]=[C:2]([C:32]3[CH:46]=[CH:45][C:35]([CH2:36][NH:37][C:38](=[O:44])[O:39][C:40]([CH3:41])([CH3:42])[CH3:43])=[CH:34][CH:33]=3)[C:3]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:4][C:5]=2[N:10]1[CH2:11][C:12]([F:15])([F:14])[F:13]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 34154424-(tert-Butoxycarbonylaminomethyl)phenylboronic acid, pinacol esterHCID 866836786-bromo-7-phenyl-1-(2,2,2-trifluoroethyl)-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-one

Product 1

HCID 86683677tert-Butyl 4-(2-oxo-7-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-6-yl)benzylcarbamateYield 85.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

In a 15 mL reaction tube was added 6-bromo-7-phenyl-1-(2,2,2-trifluoroethyl)-1H-pyrido[2,3-b][1,4]oxazin-2(3H)-one (40 mg, 0.103 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzylcarbamate (41.3 mg, 0.124 mmol), and cesium carbonate (168 mg, 0.517 mmol) in a mixture of 1,4-Dioxane (1937 μl) and water (646 μl) to give a colourless solution. This was degassed by bubbling nitrogen for 15 minutes, followed by the addition of PdCl2(dppf)-CH2Cl2Adduct (16.87 mg, 0.021 mmol) and degassing for a further 5 minutes. The reaction mixture was heated to 50° C. under a nitrogen atmosphere for one hour. LC-MS analysis showed reaction completion. The reaction mixture was allowed to cool to room temperature, diluted with water (5 mL) and extracted into ethyl acetate (3×5 mL). The combined organic phases were dried over Na2SO4, filtered and concentrated to dryness under reduced pressure to give a brown solid. The resulting residue was purified via Biotage (0-45% cyclohexane:EtOAc; 10 g column) to give the title compound (45 mg, 85%) as off-white solid. 1H NMR (500 MHz, CDCl3): 7.36 (1H, s), 7.32-7.26 (5H, m), 7.17-7.13 (4H, m), 4.96 (2H, s), 4.77 (1H, br), 4.63-4.58 (2H, q), 4.28 (2H, s), 1.48-1.45 (9H, br).

Workup

  1. customIn a 15 mL reaction tube
  2. customto give a colourless solution
  3. customThis was degassed
  4. customby bubbling nitrogen for 15 minutes
  5. customdegassing for a further 5 minutes
  6. customreaction completion
  7. temperatureto cool to room temperature
  8. extractionextracted into ethyl acetate (3×5 mL)
  9. dry with materialThe combined organic phases were dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated to dryness under reduced pressure
  12. customto give a brown solid
  13. customThe resulting residue was purified via Biotage (0-45% cyclohexane:EtOAc; 10 g column)

Sources & evidence

ORD record
ord-19008b3a4be14f6485d00777607a44ea
Source dataset
uspto-grants-2015_12
Patent number
US09221838B2

Reaction notes

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