Benzyl mercaptan → 7-(Benzylthio)-4-chloroquinoline

HRID 1473410

Reaction equation

HRID 1473410 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([Cl:12])=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.O1CCOCC1.CCN(C(C)C)C(C)C.[CH2:28]([SH:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=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].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[CH2:28]([S:35][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([Cl:12])=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

8

Reactant 4

HCID 7509Benzyl mercaptanHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 108002397-Bromo-4-Chloroquinoline

Product 1

HCID 866874577-(Benzylthio)-4-chloroquinolineYield 89%

Reagents, catalysts & solvents 3

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

Procedure

A 250-mL 3-neck round-bottom flask was charged with 7-bromo-4-chloroquinoline (BioBlocks, Inc., San Diego, Calif.; 7.000 g, 28.9 mmol), Xantphos (0.835 g, 1.443 mmol), and Pd2(dba)3 (0.661 g, 0.722 mmol), and after flushing with argon, dioxane (57.7 ml) and n,n-diisopropylethylamine (10.08 ml, 57.7 mmol) were added in sequence. The flask was fitted with a reflux condenser, and was placed in a heating bath at 80° C. for 10 minutes, after which benzyl mercaptan (3.58 ml, 30.3 mmol) was added drop wise via syringe. The reaction was stirred for 20 minutes until completion. The material was diluted with water, and washed with DCM (×3), and the combined organics were dried via phase separator (Radley's Technology) and concentrated under a vacuum. Upon dissolving the material in DCM, solids remained out of solution, and they were filtered off and washed with DCM. The corresponding filtrate was concentrated under a vacuum and purified via silica gel chromatography (120-g column) eluting with 0 to 100% ethyl acetate in heptanes to yield 7-(benzylthio)-4-chloroquinoline (7.35 g, 25.7 mmol, 89% yield) as a light yellow solid. m/z (ESI) 286.0 (M+H)+.

Workup

  1. additionwere added in sequence
  2. customThe flask was fitted with a reflux condenser
  3. washwashed with DCM (×3)
  4. customthe combined organics were dried via phase separator (Radley's Technology)
  5. concentrationconcentrated under a vacuum
  6. dissolutionUpon dissolving the material in DCM
  7. filtrationwere filtered off
  8. washwashed with DCM
  9. concentrationThe corresponding filtrate was concentrated under a vacuum
  10. custompurified via silica gel chromatography (120-g column)
  11. washeluting with 0 to 100% ethyl acetate in heptanes

Sources & evidence

ORD record
ord-ea8141a6744f44db846ca66751ba2da8
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Linked notes

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