Potassium Hydroxide → HCID 66788261, compound

HRID 576105Notes

Reaction equation

HRID 576105 reaction equation
FC(F)(F)S(O[C:7]1[CH:16]=[C:15]2[C:10]([CH:11]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=3)[CH2:12][N:13]([CH3:17])[CH2:14]2)=[CH:9][CH:8]=1)(=O)=O.[CH3:28][S:29]([C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1)(=[O:31])=[O:30].[Br-].[K+].[OH-].[K+]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:25][C:20]1[CH:19]=[C:18]([CH:11]2[C:10]3[C:15](=[CH:16][C:7]([C:35]4[CH:36]=[CH:37][C:32]([S:29]([CH3:28])(=[O:31])=[O:30])=[CH:33][CH:34]=4)=[CH:8][CH:9]=3)[CH2:14][N:13]([CH3:17])[CH2:12]2)[CH:23]=[CH:22][C:21]=1[Cl:24]

Participants

7

Reactant 4

HCID 14797Potassium HydroxideHCID 253877Potassium BromideHCID 27343644-(Methanesulfonyl)phenylboronic acidHCID 59580334HCID 59580334, compound

Product 1

HCID 66788261HCID 66788261, compoundYield 24%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-(3,4-dichlorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl trifluoromethanesulfonate (300 mg, 0.68 mmol) from Step G of Example 11, 4-(methylsulfonyl)phenylboronic acid (176 mg, 0.88 mmol), potassium bromide (243 mg, 2.04 mmol) and potassium hydroxide (114 mg, 2.04 mmol) in toluene (7 mL) was degassed with argon and then tetrakis(triphenylphosphine)palladium (0) (35 mg, 0.03 mmol) was added. The mixture was degassed again and then heated to 80° C. for 3 hours. The mixture was cooled to room temperature, diluted with dichloromethane/methanol (9:1), and filtered through a plug of silica. The filtrate was concentrated and the residue partially purified by column chromatography (hexanes to ethyl acetate) to give 4-(3,4-dichlorophenyl)-2-methyl-7-(4-(methylsulfonyl)phenyl)-1,2,3,4-tetrahydroisoquinoline (72 mg, 24%) as an off-white solid: ESI MS m/z 446 [M+H]+.

Workup

  1. customwas degassed with argon
  2. customThe mixture was degassed again
  3. temperatureThe mixture was cooled to room temperature
  4. additiondiluted with dichloromethane/methanol (9:1)
  5. filtrationfiltered through a plug of silica
  6. concentrationThe filtrate was concentrated
  7. customthe residue partially purified by column chromatography (hexanes to ethyl acetate)

Sources & evidence

ORD record
ord-21bc5b9016ad432592a26fac336418b4
Source dataset
uspto-grants-2015_05
Patent number
US09034899B2

Reaction notes

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