Triphenylphosphine → 8-{4-Fluoro-3-[2-(4-methanesulfonyl-phenyl)-vinyl]-phenyl}-6-isopropyl-quinoline

HRID 896701Notes

Reaction equation

HRID 896701 reaction equation
[CH3:1][S:2]([C:5]1[CH:12]=[CH:11][C:8]([CH2:9]Cl)=[CH:7][CH:6]=1)(=[O:4])=[O:3].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[K+].[F:38][C:39]1[CH:46]=[CH:45][C:44]([C:47]2[CH:48]=[C:49]([CH:57]([CH3:59])[CH3:58])[CH:50]=[C:51]3[C:56]=2[N:55]=[CH:54][CH:53]=[CH:52]3)=[CH:43][C:40]=1[CH:41]=O>C(#N)C.C1COCC1.Cl.C(OCC)(=O)C>[F:38][C:39]1[CH:46]=[CH:45][C:44]([C:47]2[CH:48]=[C:49]([CH:57]([CH3:58])[CH3:59])[CH:50]=[C:51]3[C:56]=2[N:55]=[CH:54][CH:53]=[CH:52]3)=[CH:43][C:40]=1[CH:41]=[CH:9][C:8]1[CH:11]=[CH:12][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:6][CH:7]=1

Participants

9

Reactant 4

HCID 11776TriphenylphosphineHCID 1235301-(Chloromethyl)-4-methanesulfonylbenzeneHCID 223500542-Fluoro-5-(6-isopropylquinolin-8-yl)-benzaldehydeHCID 23665647Potassium tert-butoxide

Product 1

HCID 696938948-{4-Fluoro-3-[2-(4-methanesulfonyl-phenyl)-vinyl]-phenyl}-6-isopropyl-quinoline

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
21 °C

Procedure

A solution of 4-methanesulfonylbenzyl chloride (10 g, 49 mmol) and triphenylphosphine (12.8 g, 49 mmol) in acetonitrile (100 mL) was stirred for 18 h at reflux. The resulting reaction mixture was cooled to 21° C. and the phosphorus salt crystallised from CH3CN/ether. To a suspension of the salt (875 mg, 1.87 mmol) in THF (15 mL) at 0° C. was added potassium tert-butoxide (1M, THF, 1.87 mL, 1.87 mmol) dropwise and the resulting mixture stirred 30 min at 0° C. The mixture was cooled to −78° C. and the 2-fluoro-5-(6-isopropyl-quinolin-8-yl)-benzaldehyde from Step 3 (0.5 g, 1.7 mmol, in THF) was added. After 90 min. at 21° C., the reaction mixture was diluted with HCl 10% and ethyl acetate. The organic extracts were washed (H2O, brine), dried (MgSO4), filtered and concentrated. Purification by flash chromatography (eluting with hexane/ethyl acetate, 60:40) provided the 8-{4-fluoro-3-[2-(4-methanesulfonyl-phenyl)-vinyl]-phenyl}-6-isopropyl-quinoline compound as a mixture of isomer (3:1).

Workup

  1. temperatureat reflux
  2. customThe resulting reaction mixture
  3. customthe phosphorus salt crystallised from CH3CN/ether
  4. temperatureThe mixture was cooled to −78° C.
  5. waitAfter 90 min. at 21° C.
  6. washThe organic extracts were washed (H2O, brine)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification
  11. washby flash chromatography (eluting with hexane/ethyl acetate, 60:40)

Sources & evidence

ORD record
ord-da0ccde486a447d5a944bd46bd0d512b
Source dataset
uspto-grants-2005_07
Patent number
US06919353B2

Reaction notes

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