Water → 6-(benzylthio)-1-(5-ethoxy-2,3'-difluoro-[1,1'-biphenyl]-4-yl)quinolin-2(1 H)-one

HRID 1504444Notes

Reaction equation

HRID 1504444 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]([OH:25])=[CH:23][C:22]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=3)=[C:21]([F:33])[CH:20]=1)[C:14](=[O:34])[CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].I[CH2:42][CH3:43].O>CN(C=O)C>[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][CH2:42][CH3:43])=[CH:23][C:22]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=3)=[C:21]([F:33])[CH:20]=1)[C:14](=[O:34])[CH:13]=[CH:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6340IodoethaneHCID 11430Potassium CarbonateHCID 1177369776-(Benzylthio)-1-(2,3'-difluoro-5-hydroxy-[1,1'-biphenyl]-4-yl)quinolin-2(1H)-one

Product 1

HCID 1177371246-(benzylthio)-1-(5-ethoxy-2,3'-difluoro-[1,1'-biphenyl]-4-yl)quinolin-2(1 H)-oneYield 99%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6-(Benzylthio)-1-(2,3′-difluoro-5-hydroxy-[1,1′-biphenyl]-4-yl)quinolin-2(1H)-one (510 mg, 1.082 mmol) was dissolved in DMF (2163 μl). Then potassium carbonate (149 mg, 1.082 mmol) was added followed by iodoethane (96 μl, 1.190 mmol). After stirring at rt for 1 d, water was added. A gummy solid was collected with an aid of water, and dried. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 0% to 50% EtOAc in heptane, to provide 6-(benzylthio)-1-(5-ethoxy-2,3′-difluoro-[1,1′-biphenyl]-4-yl)quinolin-2(1 H)-one (534 mg, 99% yield) as white solid. Ink (ESI) [M+H]+=500.0. NMR (400 MHz, DMSO-d6) δ ppm 1.00 (t, J=6.94 Hz, 3 H) 4.01-4.13 (m, 2 H) 4.24 (s, 2 H) 6.60 (d, J=8.80 Hz, 1 H) 6.70 (d, J=9.59 Hz, 1 H) 7.18-7.35 (m, 6 H) 7.38-7.48 (m, 3 H) 7.49-7.63 (m, 3 H) 7.79 (d, J=2.15 Hz, 1 H) 7.96 (d, J=9.59 Hz, 1 H).

Workup

  1. customA gummy solid was collected with an aid of water
  2. customdried
  3. customThe crude material was absorbed onto a plug of silica gel
  4. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (40 g)
  5. washeluting with a gradient of 0% to 50% EtOAc in heptane

Sources & evidence

ORD record
ord-0242f4cd0faf423a9f746b16765165e4
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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