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

HRID 870125Notes

Reaction equation

HRID 870125 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:17]=[C:18]([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:19]=[CH:20][CH:21]=1.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>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]>[CH2:13]([S:14][C:20]1[CH:19]=[C:18]([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:17]=[CH:16][CH:21]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

7

Reactant 4

HCID 7509Benzyl mercaptanHCID 11430Potassium CarbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 223869034-(3-Bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline

Product 1

HCID 674541794-(3-(Benzylthio)phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline

Reagents, catalysts & solvents 2

HCID 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 a solution of potassium carbonate (930 mg, 0.50 equiv) in xylene (50 mL). This was followed by the addition of phenylmethanethiol (2.5 g, 1.50 equiv) dropwise with stirring at 0° C. The resulting solution was stirred for 1 h at 25° C. Into another 100-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was added a solution of 4-(3-bromophenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline (5.0 g, 1 equiv) in xylene (50 mL), Pd2(dba)3 (300 mg), Xantphos (300 mg). The resulting solution was stirred for 30 min at 25° C. and then added to the above reaction solution. The mixture was stirred overnight at 140° C. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:100˜1:50). This resulted in 2.5 g (45%) of 4-(3-(benzylthio)phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline as a yellow oil.

Workup

  1. customInto a 250-mL 3-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. stirringThe resulting solution was stirred for 1 h at 25° C
  4. customInto another 100-mL 3-necked round-bottom flask purged
  5. temperaturemaintained with an inert atmosphere of nitrogen
  6. stirringThe resulting solution was stirred for 30 min at 25° C.
  7. additionadded to the above reaction solution
  8. stirringThe mixture was stirred overnight at 140° C
  9. concentrationThe resulting mixture was concentrated under vacuum
  10. customThis resulted in 2.5 g (45%) of 4-(3-(benzylthio)phenyl)-6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinoline as a yellow oil

Sources & evidence

ORD record
ord-5009748019c24362bc02188cff29b621
Source dataset
uspto-grants-2015_03
Patent number
US08969377B2

Reaction notes

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