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

HRID 2047909Notes

Reaction equation

HRID 2047909 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-4aadedc3b1b44f9db4b25608f218b7f2
Source dataset
uspto-grants-2013_11
Patent number
US08592597B2

Reaction notes

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