Sodium Carbonate → HCID 9857366, compound

HRID 1725064Notes

Reaction equation

HRID 1725064 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6](Br)=[CH:5][C:4]=1[F:10])#[N:2].[CH3:11][C:12]1([CH3:26])[C:17]2[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][C:16]=2[NH:15][C:14](=[O:25])[O:13]1.C(=O)([O-])[O-].[Na+].[Na+].[OH-].[Na+]>COCCOC.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:1]([C:3]1[CH:8]=[CH:7][C:6]([C:19]2[CH:20]=[CH:21][C:16]3[NH:15][C:14](=[O:25])[O:13][C:12]([CH3:26])([CH3:11])[C:17]=3[CH:18]=2)=[CH:5][C:4]=1[F:10])#[N:2]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 7360294-Bromo-2-fluorobenzonitrileHCID 10987806(4,4-Dimethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)boronic acid

Product 1

HCID 9857366HCID 9857366, compoundYield 6%

Reagents, catalysts & solvents 3

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

Procedure

A solution of 4-cyano-3-fluoro-bromobenzene (0.6 g, 3.0 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.2 g) in ethylene glycol dimethyl ether (20 mL) was stirred under N2 for 20 minutes. To this mixture was then added (1,4-dihydro-4,4-dimethyl-2-oxo-2H-3,1-benzoxazin-6-yl)boronic acid (1.0 g, 4.5 mmol) and sodium carbonate (1.1 g, 10.6 mmol) in water (5 mL). The solution was brought to reflux for 18 hours and then cooled to room temperature, poured into 2N NaOH and extracted with EtOAc (3×50 mL). The combined extracts were washed with water, brine, dried (MgSO4), and evaporated. The residue was purified by column chromatography (SiO2, EtOAc:hexane=1:2) to afford the title compound (0.05 g, 6%) as an off-white solid. mp: 272-275° C.; 1H-NMR (DMSO-d6) δ 10.4 (s, 1H), 8.0 (t, 1 H, J=7.7 Hz), 7.9 (dd, 1H, J=10.3, 1.3 Hz), 7.8 (dd, 1H, J=6.8, 1.4 Hz), 7.7 (m, 2H), 6.9 (d, 1H, J=8.9 Hz), 1.7 (s, 6H); MS (EI) M+@m/z 296.

Workup

  1. temperatureto reflux for 18 hours
  2. extractionextracted with EtOAc (3×50 mL)
  3. washThe combined extracts were washed with water, brine
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe residue was purified by column chromatography (SiO2, EtOAc:hexane=1:2)

Sources & evidence

ORD record
ord-431cfc9f09324fb089ef1c4176e49032
Source dataset
uspto-grants-2009_02
Patent number
US07488822B2

Reaction notes

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