Chlorosulfonic acid → 4-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-benzenesulfonyl chloride

HRID 1072503Notes

Reaction equation

HRID 1072503 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[CH2:8][N:7]([CH3:13])[CH2:6][CH:5]2[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[Cl:20][S:21](O)(=[O:23])=[O:22]>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[CH2:8][N:7]([CH3:13])[CH2:6][CH:5]2[C:14]1[CH:15]=[CH:16][C:17]([S:21]([Cl:20])(=[O:23])=[O:22])=[CH:18][CH:19]=1

Participants

3

Reactant 2

HCID 24638Chlorosulfonic acidHCID 223868076,8-Dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline2×

Product 1

HCID 223868894-(6,8-Dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-benzenesulfonyl chloride

Conditions

Temperature
40 °C

Procedure

6,8-Dichloro-2-methyl-4-phenyl-1,2,3,4-tetrahydro-isoquinoline (intermediate 4, example 2) was introduced in portions into chlorosulfonic acid (6.6 ml). The mixture was subsequently stirred at 40° C. for one hour. The reaction mixture was then cooled to room temperature and an ice/water mixture was added. The precipitate which separated out during this was filtered off with suction and taken up in ethyl acetate which, after washing with saturated brine was dried over magnesium sulfate. Subsequent concentration afforded 4-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-benzenesulfonyl chloride as a solid crude product, a portion of which (150 mg) was directly introduced in portions into dimethylamine solution (5 ml, approx. 40% in water) cooled to 10° C. The resulting suspension was subsequently stirred at this temperature for 1.5 h. Then ice-water was added and, after extraction three times with ethyl acetate, the combined ethyl acetate phases were washed with saturated brine and dried over magnesium sulfate. The residue was taken up with water and, after addition of 2 N HCl, freeze dried. The crude product obtained in this way was then purified by preparative HPLC.

Workup

  1. temperatureThe reaction mixture was then cooled to room temperature
  2. customThe precipitate which separated out during
  3. filtrationthis was filtered off with suction
  4. washafter washing with saturated brine
  5. dry with materialwas dried over magnesium sulfate
  6. concentrationSubsequent concentration

Sources & evidence

ORD record
ord-03a3abd3bb4746e893fd8039ce83eaa8
Source dataset
uspto-grants-2005_06
Patent number
US06911453B2

Reaction notes

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