Boron tribromide → 6-(Benzylthio)-1-(2,3'-difluoro-5-hydroxy-[1,1'-biphenyl]-4-yl)quinolin-2(1H)-one

HRID 1504499Notes

Reaction equation

HRID 1504499 reaction equation
[CH2:1]([S:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N:15]([C:19]1[C:24]([O:25]C)=[CH:23][C:22]([C:27]3[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[CH:28]=3)=[C:21]([F:34])[CH:20]=1)[C:14](=[O:35])[CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B(Br)(Br)Br>>[CH2:1]([S:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N:15]([C:19]1[C:24]([OH:25])=[CH:23][C:22]([C:27]3[CH:32]=[CH:31][CH:30]=[C:29]([F:33])[CH:28]=3)=[C:21]([F:34])[CH:20]=1)[C:14](=[O:35])[CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 25134Boron tribromideHCID 1177369956-(benzylthio)-1-(2,3'-difluoro-5-methoxy-[1,1'-biphenyl]-4-yl)quinolin-2(1H)-one

Product 1

HCID 1177369776-(Benzylthio)-1-(2,3'-difluoro-5-hydroxy-[1,1'-biphenyl]-4-yl)quinolin-2(1H)-oneYield 86%

Procedure

To a solution of 6-(benzylthio)-1-(2,3′-difluoro-5-methoxy-[1,1′-biphenyl]-4-yl)quinolin-2(1H)-one (1.700 g, 3.50 mmol) was added boron tribromide (1.0 M in DCM) (17.51 ml, 17.51 mmol) at rt to give a dark solution and stirred for 1 h. The whole was poured on to ice-water mixture. The product was extracted with DCM (3×30 mL). The organic layer was separated, combined, dried over MgSO4, filtered, and concentrated to afford beige solid. The solid was triturated with a mixture of EtOAc/Et2O. The solid was filtered with an aid of Et2O. 1.32 g was obtained. A second batch was obtained from the filtrate. The filtrate was concentrated. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g), eluting with a gradient of 0% to 50% EtOAc in heptane, to provide 6-(benzylthio)-1-(2,3′-difluoro-5-hydroxy-[1,1′-biphenyl]-4-yl)quinolin-2(1 H)-one (1.42 g, 80% yield) as light brown solid. m/z (ESI): [M+H]+=472.0. 1 H NMR (400 MHz, DMSO-d6) □ppm 4.24 (s, 2 H) 6.63 (d, J=8.80 Hz, 1 H) 6.69 (d, J=9.59 Hz, 1 H) 7.15 (d, J=7.34 Hz, 1 H) 7.18-7.37 (m, 7 H) 7.38-7.48 (m, 3 H) 7.57 (dd, J=8.02, 6.06 Hz, 1 H) 7.79 (d, J=2.15 Hz, 1 H) 7.95 (d, J=9.49 Hz, 1H) 9.97 (s, 1 H).

Workup

  1. customto give a dark solution
  2. extractionThe product was extracted with DCM (3×30 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford beige solid
  8. customThe solid was triturated with a mixture of EtOAc/Et2O
  9. filtrationThe solid was filtered with an aid of Et2O
  10. custom1.32 g was obtained
  11. customA second batch was obtained from the filtrate
  12. concentrationThe filtrate was concentrated
  13. customThe crude material was absorbed onto a plug of silica gel
  14. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (12 g)
  15. washeluting with a gradient of 0% to 50% EtOAc in heptane

Sources & evidence

ORD record
ord-d96d745f606c44c58bd2650dfcb75e17
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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