Chlorosulfonic acid → 4-(4-((R)-2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)propanoyl)piperazin-1-yl)benzene-1-sulfonyl chloride

HRID 1876645Notes

Reaction equation

HRID 1876645 reaction equation
[Cl:1][S:2]([OH:5])(=O)=[O:3].[Cl:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]([C@H:17]([CH3:32])[C:18]([N:20]1[CH2:25][CH2:24][N:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:22][CH2:21]1)=[O:19])[CH2:12][CH2:11][CH2:10]2>>[Cl:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]([C@H:17]([CH3:32])[C:18]([N:20]1[CH2:21][CH2:22][N:23]([C:26]3[CH:27]=[CH:28][C:29]([S:2]([Cl:1])(=[O:5])=[O:3])=[CH:30][CH:31]=3)[CH2:24][CH2:25]1)=[O:19])[CH2:12][CH2:11][CH2:10]2

Participants

3

Reactant 2

HCID 24638Chlorosulfonic acidHCID 33590812(R)-2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)-1-(4-phenylpiperazin-1-yl)propan-1-one

Product 1

HCID 536276014-(4-((R)-2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)propanoyl)piperazin-1-yl)benzene-1-sulfonyl chlorideYield 10%

Procedure

To a 0° C. solution of chlorosulfonic acid, was added (R)-2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)-1-(4-phenylpiperazin-1-yl)propan-1-one over 5 minutes. The resultant solution was heated to 120° C. for 2 hrs. The reaction mixture was cooled and carefully poured into ice-water (750 mL). The solution was extracted with methylene chloride (4×250 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated. Purification via silica gel chromatography using 40-70% ethyl acetate in hexane gave 4-(4-((R)-2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)propanoyl)piperazin-1-yl)benzene-1-sulfonyl chloride as a yellow oil (760 mg, 10%). LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=482.3; tR=3.65 min.

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionThe solution was extracted with methylene chloride (4×250 mL)
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification via silica gel chromatography

Sources & evidence

ORD record
ord-202f6a2702674d319af217b17a253dce
Source dataset
uspto-grants-2012_11
Patent number
US08309587B2

Reaction notes

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