Benzyl mercaptan → 4-(4-(Benzylthio)phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline

HRID 870147Notes

Reaction equation

HRID 870147 reaction equation
C([O-])([O-])=O.[K+].[K+].[C:7]1([CH2:13][SH:14])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.Br[C:16]1[CH:21]=[CH:20][C:19]([CH:22]2[C:31]3[C:26](=[C:27]([Cl:33])[CH:28]=[C:29]([Cl:32])[CH:30]=3)[CH2:25][N:24]([CH3:34])[CH2:23]2)=[CH:18][CH:17]=1>C1(C)C(C)=CC=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.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>[CH2:13]([S:14][C:16]1[CH:17]=[CH:18][C:19]([CH:22]2[C:31]3[C:26](=[C:27]([Cl:33])[CH:28]=[C:29]([Cl:32])[CH:30]=3)[CH2:25][N:24]([CH3:34])[CH2:23]2)=[CH:20][CH:21]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

7

Reactant 3

HCID 7509Benzyl mercaptanHCID 11430Potassium CarbonateHCID 101772114-(4-Bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline

Product 1

HCID 674572634-(4-(Benzylthio)phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolineYield 33.6%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 7237O-XyleneSolvent2×

Conditions

Temperature
0 °C

Procedure

Into a 250-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed K2CO3 (800 mg, 0.50 equiv) and xylene (50 mL). This was followed by the addition of phenylmethanethiol (1.75 g, 1.00 equiv) dropwise with stirring at 0° C. The resulting mixture was then allowed to warm to room temperature and stirred for 1 h. Into another 250-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 4-(4-bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline (4.8 g, 0.80 equiv), Xantphos (200 mg, 0.08 equiv) and Pd2(dba)3 (200 mg, 0.08 equiv) in xylene (30 mL). The mixture was stirred at room temperature for 20 min and transferred to the previously formed potassium thiolate. The dark solution was then purged with nitrogen and heated to 130° C. for 15 h. After cooling to room temperature, the mixture was concentrated under reduced pressure. The crude product was then purified by silica gel chromatography with ethyl acetate/petroleum ether (1:80˜1:50) to afford 1.8 g (30%) of the title compound as yellow oil. MS (ES, m/z): 414 [M+H]+.

Workup

  1. customInto a 250-mL 3-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. temperatureto warm to room temperature
  4. stirringstirred for 1 h
  5. customInto another 250-mL 3-necked round-bottom flask purged
  6. temperaturemaintained with an inert atmosphere of nitrogen
  7. stirringThe mixture was stirred at room temperature for 20 min
  8. customThe dark solution was then purged with nitrogen
  9. temperatureheated to 130° C. for 15 h
  10. temperatureAfter cooling to room temperature
  11. concentrationthe mixture was concentrated under reduced pressure
  12. customThe crude product was then purified by silica gel chromatography with ethyl acetate/petroleum ether (1:80˜1:50)

Sources & evidence

ORD record
ord-593e2e1ee1094180aad527c22e910031
Source dataset
uspto-grants-2015_03
Patent number
US08969377B2

Reaction notes

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