Benzyl mercaptan → 3-(Benzylsulfanyl)-5-fluoropyridine

HRID 880849Notes

Reaction equation

HRID 880849 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([F:8])[CH:7]=1.[C:9]1([CH2:15][SH:16])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C(N(CC)C(C)C)(C)C>C1(C)C=CC=CC=1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>[CH2:15]([S:16][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([F:8])[CH:7]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

8

Reactant 3

HCID 7509Benzyl mercaptanHCID 81531DiisopropylethylamineHCID 8202063-Bromo-5-fluoropyridine

Product 1

HCID 583498303-(Benzylsulfanyl)-5-fluoropyridineYield 90.3%

Reagents, catalysts & solvents 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 3-bromo-5-fluoropyridine (522 mg) in toluene (5 mL) were added phenylmethanethiol (370 mg), N,N-diisopropylethylamine (831 mg), tris(dibenzylideneacetone)dipalladium(0) (108 mg) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (138 mg), and the mixture was stirred under an argon atmosphere at 80° C. for 2 hr. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and filtered through silica gel. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent:hexane→hexane-ethyl acetate=10:1) to give the title compound as an orange oil (yield 587 mg, 90%).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered through silica gel
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (eluent:hexane→hexane-ethyl acetate=10:1)

Sources & evidence

ORD record
ord-476244ec1d2043048e457087e58a81f2
Source dataset
uspto-grants-2015_03
Patent number
US08993598B2

Reaction notes

Loading…