Nitrogen → HCID 86710769, compound

HRID 1400718Notes

Reaction equation

HRID 1400718 reaction equation
[F:1][C:2]1[C:7]2[O:8][CH2:9][CH2:10][NH:11][C:6]=2[CH:5]=[C:4]([B:12]2[O:16][C:15]([CH3:18])([CH3:17])[C:14]([CH3:20])([CH3:19])[O:13]2)[CH:3]=1.C([O-])([O-])=O.[K+].[K+].N#N.[CH2:29](Br)[CH:30]=[CH2:31]>CN(C=O)C.O>[CH2:31]([N:11]1[CH2:10][CH2:9][O:8][C:7]2[C:2]([F:1])=[CH:3][C:4]([B:12]3[O:16][C:15]([CH3:18])([CH3:17])[C:14]([CH3:20])([CH3:19])[O:13]3)=[CH:5][C:6]1=2)[CH:30]=[CH2:29]

Participants

7

Reactant 4

HCID 947NitrogenHCID 7841Allyl bromideHCID 11430Potassium CarbonateHCID 567767168-Fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-1,4-benzoxazine

Product 1

HCID 86710769HCID 86710769, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 8-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine (0.507 g, 1.613 mmol, Ref. WO20100130034) and K2CO3 (0.512 g, 3.70 mmol) in dry DMF (5 mL) was sparged with N2 for 5 min, then treated with allyl bromide (0.8 mL, 9.17 mmol). The reaction tube was sealed and then heated (70° C.) for 22 h. The reaction was cooled then diluted with water (50 mL) and extracted into EtOAc (50 mL). The organic layer was then washed with water, brine, dried (Na2SO4), filtered, and concentrated. The residue was purified by biotage column chromatography (12 g SiO2, 0% (3 CV); 0-40% (15 CV), 40% (2 CV), EtOAc in hexanes) to afford the desired product (0.396 g, 1.241 mmol, 77% yield) as a clear viscous oil. 1H NMR (500 MHz, CDCl3) δ 6.96-7.01 (m, 2H), 5.84-5.95 (m, 1H), 5.21-5.32 (m, 2H), 4.32-4.38 (m, 2H), 3.94 (d, J=5.8 Hz, 2H), 3.30-3.37 (m, 2H), 1.32 (s, 12H). LCMS (M+H)=320.3.

Workup

  1. customThe reaction tube was sealed
  2. temperatureThe reaction was cooled
  3. extractionextracted into EtOAc (50 mL)
  4. washThe organic layer was then washed with water, brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by biotage column chromatography (12 g SiO2, 0% (3 CV); 0-40% (15 CV), 40% (2 CV), EtOAc in hexanes)

Sources & evidence

ORD record
ord-10f534619fe2422da579142f5a6a738f
Source dataset
uspto-grants-2014_12
Patent number
US08906929B2

Reaction notes

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