Hydrochloric Acid → (3S)-3-ethyl-6-fluoro-4-[(4-hydroxyphenyl)sulfonyl]-1-propyl-3,4-dihydroquinoxalin-2(1H)-one

HRID 898251Notes

Reaction equation

HRID 898251 reaction equation
C(=O)([O:5][C:6]1[CH:11]=[CH:10][C:9]([S:12]([N:15]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([F:25])[CH:23]=3)[NH:18][C:17](=[O:26])[C@@H:16]2[CH2:27][CH3:28])(=[O:14])=[O:13])=[CH:8][CH:7]=1)OCC.C(=O)([O-])[O-].[Cs+].[Cs+].I[CH2:37][CH2:38][CH3:39].[OH-].[Na+].Cl>CC(C)=O>[CH2:27]([C@@H:16]1[N:15]([S:12]([C:9]2[CH:10]=[CH:11][C:6]([OH:5])=[CH:7][CH:8]=2)(=[O:14])=[O:13])[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([F:25])[CH:23]=2)[N:18]([CH2:37][CH2:38][CH3:39])[C:17]1=[O:26])[CH3:28]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 14798Sodium HydroxideHCID 336431-IodopropaneHCID 69224101ethyl 4-{[(2S)-2-ethyl-7-fluoro-3-oxo-3,4-dihydroquinoxalin-1(2H)-yl]sulfonyl}phenyl carbonate

Product 1

HCID 11538398(3S)-3-ethyl-6-fluoro-4-[(4-hydroxyphenyl)sulfonyl]-1-propyl-3,4-dihydroquinoxalin-2(1H)-oneYield 30.7%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
62 °C

Procedure

To a solution of ethyl 4-{[(2S)-2-ethyl-7-fluoro-3-oxo-3,4-dihydroquinoxalin-1(2H)-yl]sulfonyl}phenyl carbonate (0.35 g, 0.83 mmol) in acetone (5 mL) was added cesium carbonate (0.3 g, 0.91 mmol), and 1-iodopropane (0.32 ml, 3.32 mmol). The mixture was heated at 62° C. for 2.5 hours, cooled to 25° C., and treated with a 2N aqueous solution of sodium hydroxide (3 mL). The reaction was then stirred at 25° C. for 2 hours, and was acidified to pH<2 with the addition of a 2N aqueous solution of hydrochloric acid. The resulting mixture was partitioned between ethyl acetate and a saturated aqueous solution of sodium chloride. The organic layer was separated, dried over magnesium sulfate, and concentrated. The product was purified via flash column chromatography (SiO2, 30% ethyl acetate:hexane eluted to 60% ethyl acetate:hexane) to afford 0.1 g (3S)-3-ethyl-6-fluoro-4-[(4-hydroxyphenyl)sulfonyl]-1-propyl-3,4-dihydroquinoxalin-2(1H)-one as a white solid. MS (ESI) m/z 393 ([M+H]+); MS (ESI) m/z 391 ([M−H]−); Anal. Calcd for C19H21FN2O4S: C, 58.15; H, 5.39; N, 7.14. Found: C, 57.95; H, 5.46; N, 6.66.

Workup

  1. temperaturecooled to 25° C.
  2. customThe resulting mixture was partitioned between ethyl acetate
  3. customThe organic layer was separated
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe product was purified via flash column chromatography (SiO2, 30% ethyl acetate:hexane eluted to 60% ethyl acetate:hexane)

Sources & evidence

ORD record
ord-abe54c9b8f254840b370f598eb337471
Source dataset
uspto-grants-2008_04
Patent number
US07351709B2

Reaction notes

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