Tetrahydrofuran → HCID 89782033, compound

HRID 1056220Notes

Reaction equation

HRID 1056220 reaction equation
[C:1]([NH:5][C:6]1[C:7]([F:19])=[N:8][C:9]2[C:14]([N:15]=1)=[C:13]([C:16](=[O:18])[CH3:17])[CH:12]=[CH:11][CH:10]=2)([CH3:4])([CH3:3])[CH3:2].FC(F)(F)S(O[Si](C(C)(C)C)(C)C)(=O)=O.C1COCC1.C1C(=O)N([Br:47])C(=O)C1>C(Cl)Cl.O>[Br:47][CH2:17][C:16]([C:13]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:14]=1[N:15]=[C:6]([NH:5][C:1]([CH3:4])([CH3:2])[CH3:3])[C:7]([F:19])=[N:8]2)=[O:18]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 67184N-bromobutanimideHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 89782158HCID 89782158, compound

Product 1

HCID 89782033HCID 89782033, compoundYield 58.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

A solution of 1-(3-(tert-butylamino)-2-fluoroquinoxalin-5-yl)ethanone (343b) (113 mg, 0.43 mmol), tert-butyldimethylsilyl trifluoromethanesulfonate (149 μL, 0.65 mmol), and TEA (181 μL, 1.29 mmol) in DCM (4.3 mL) was stirred at 0° C. for 30 min when silyl enol ether was observed via lcms. The reaction mixture was diluted with DCM (100 mL), added to a separatory funnel, and washed with saturated aq. NaHCO3 (75 mL) before the organic layer was separated, dried over Na2SO4, and concentrated to give an oil. To a solution of the resulting oil in water (0.13 mL) and THF (4.3 mL) at RT was added NBS (92 mg, 0.52 mmol) and stirred for 1 h. The reaction mixture was diluted with DCM (100 mL), added to a separatory funnel, and washed with saturated aq. NaHCO3 (75 mL) before the organic layer was separated, dried over Na2SO4, and concentrated. The crude product was adsorbed onto silica and was purified via automated flash chromatography (silica gel) with 0-15% EtOAc in hexanes to give 2-bromo-1-(3-(tert-butylamino)-2-fluoroquinoxalin-5-yl)ethanone (343c) (85 mg, 0.25 mmol, 58% yield) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ ppm 1.58 (s, 9H) 4.94 (s, 2H) 5.41 (br. s., 1H) 7.44 (t, J=7.82 Hz, 1H) 7.87 (dd, J=8.02, 1.57 Hz, 1H) 7.92 (dd, J=7.43, 1.37 Hz, 1H). 19F NMR (377 MHz, CDCl3) δ ppm −79.69 (s, 1F). MS (ESI, pos. ion) m/z: 340.2/342.2 (M+1).

Workup

  1. additionadded to a separatory funnel
  2. washwashed with saturated aq. NaHCO3 (75 mL) before the organic layer
  3. customwas separated
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customto give an oil
  7. additionadded to a separatory funnel
  8. washwashed with saturated aq. NaHCO3 (75 mL) before the organic layer
  9. customwas separated
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated
  12. customwas purified

Sources & evidence

ORD record
ord-0d77f50a8b5d4f8b8eadd947c7aec05a
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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