Benzyl mercaptan → 6-(Benzylthio)-1-chloroisoquinoline

HRID 1473371Notes

Reaction equation

HRID 1473371 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([Cl:12])=[N:7][CH:6]=[CH:5]2.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.CCN(C(C)C)C(C)C.[CH2:64]([SH:71])[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1>CCCCCCC.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].O1CCOCC1>[CH2:64]([S:71][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([Cl:12])=[N:7][CH:6]=[CH:5]2)[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1

Participants

8

Reactant 4

HCID 7509Benzyl mercaptanHCID 81531DiisopropylethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 222502446-Bromo-1-chloro-isoquinoline

Product 1

HCID 866874176-(Benzylthio)-1-chloroisoquinoline

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8900HeptaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A round-bottom flask was charged with 6-bromo-1-chloro-isoquinoline (1.574 ml, 10.86 mmol), Xantphos (0.314 g, 0.543 mmol), and Pd2(dba)3 (0.249 g, 0.271 mmol). The flask was flushed with Ar (g), then 1,4-dioxane (21.72 ml), n,n-diisopropylethylamine (3.79 ml, 21.72 mmol), and benzyl mercaptan (1.349 ml, 11.40 mmol) were added in sequence. The flask was fitted with a reflux condenser and heated to 80° C. for 1 h. The mixture was cooled and concentrated under a vacuum. The crude product was purified by chromatography on silica gel (80-g Redi-Sep Gold column, 25-g silica gel loading column, 0-40% EtOAc/Heptane) to give a yellow solid. The solid was suspended in heptane, sonicated, and filtered. The collected solid was washed with heptane, dried under a stream of N2 (g), then dried under vacuum for to give 6-(benzylthio)-1-chloroisoquinoline as an off-white powder: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm=8.26-8.10 (m, 2H), 7.63-7.51 (m, 2H), 7.46-7.39 (m, 3H), 7.37-7.28 (m, 3H), 4.31 (s, 2H); m/z (ESI) 286.2 (M+H)+.

Workup

  1. customThe flask was flushed with Ar (g)
  2. customThe flask was fitted with a reflux condenser
  3. temperatureThe mixture was cooled
  4. concentrationconcentrated under a vacuum
  5. customThe crude product was purified by chromatography on silica gel (80-g Redi-Sep Gold column, 25-g silica gel loading column, 0-40% EtOAc/Heptane)
  6. customto give a yellow solid
  7. customsonicated
  8. filtrationfiltered
  9. washThe collected solid was washed with heptane
  10. dry with materialdried under a stream of N2 (g)
  11. customdried under vacuum for

Sources & evidence

ORD record
ord-bfbafcf481e846feb040d2c0514660dc
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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