Benzyl mercaptan → 6-(Benzylthio)-3-chloroisoquinoline

HRID 1473385Notes

Reaction equation

HRID 1473385 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][C:6]([Cl:12])=[CH:5]2.O1CCOCC1.C(N(CC)C(C)C)(C)C.[CH2:28]([SH:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>CCOC(C)=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:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][C:6]([Cl:12])=[CH:5]2)[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 226075306-Bromo-3-chloroisoquinoline

Product 1

HCID 866874276-(Benzylthio)-3-chloroisoquinolineYield 89.1%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A pressure vessel was charged with 6-bromo-3-chloroisoquinoline (1.3307 g, 5.49 mmol), Xantphos (0.159 g, 0.274 mmol), and Pd2(dba)3 (0.126 g, 0.137 mmol). The vessel was flushed with Ar (g), then 1,4-dioxane (10.97 ml), N,N-diisopropylethylamine (1.917 ml, 10.97 mmol), and benzyl mercaptan (0.682 ml, 5.76 mmol) were added in sequence. The vessel was sealed and heated in an 80° C. heating bath for 16 h. The mixture was cooled, diluted with EtOAc, and filtered through diatomaceous earth. The filtrate was concentrated, and the residue was purified by chromatography on silica gel (25-g silica gel loading column, 0 to 30% EtOAC/Heptane) to give 6-(benzylthio)-3-chloroisoquinoline (1.398 g, 4.89 mmol, 89% yield) as a light-yellow solid: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm=8.94 (s, 1H), 7.81 (d, J=8.6 Hz, 1H), 7.55 (d, J=0.2 Hz, 1H), 7.50-7.39 (m, 4H), 7.38-7.28 (m, 3H), 4.30 (s, 2H); m/z (ESI) 286.2 (M+H)+.

Workup

  1. customThe vessel was flushed with Ar (g)
  2. customThe vessel was sealed
  3. temperatureheating bath for 16 h
  4. temperatureThe mixture was cooled
  5. filtrationfiltered through diatomaceous earth
  6. concentrationThe filtrate was concentrated
  7. customthe residue was purified by chromatography on silica gel (25-g silica gel loading column, 0 to 30% EtOAC/Heptane)

Sources & evidence

ORD record
ord-7bbb2550e8904722a16acce06868f82b
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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