Dichloromethane → N-(3,5-dichlorobenzenesulfonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, methyl ester

HRID 411743Notes

Reaction equation

HRID 411743 reaction equation
Cl.[CH2:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][CH:4]([C:12]([O:14][CH3:15])=[O:13])[NH:3]1.C(Cl)Cl.CCN(C(C)C)C(C)C.[Cl:28][C:29]1[CH:30]=[C:31]([S:36](Cl)(=[O:38])=[O:37])[CH:32]=[C:33]([Cl:35])[CH:34]=1>CN(C1C=CN=CC=1)C.C(OCC)(=O)C.CCCCCC.C1COCC1>[Cl:35][C:33]1[CH:32]=[C:31]([S:36]([N:3]2[CH:4]([C:12]([O:14][CH3:15])=[O:13])[CH2:5][C:6]3[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=3)[CH2:2]2)(=[O:37])=[O:38])[CH:30]=[C:29]([Cl:28])[CH:34]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 81531Diisopropylethylamine2×HCID 5223883,5-Dichlorobenzenesulfonyl chlorideHCID 122480673-Isoquinolinecarboxylic acid, 1,2,3,4-tetrahydro-, methyl ester, hydrochloride (1:1)

Product 1

HCID 86586601N-(3,5-dichlorobenzenesulfonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, methyl esterYield 80.2%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, methyl ester hydrochloride (200 mg, 0.878 mmol) in a 1:1 mixture of CH2Cl2 and THF (2.5 mL each) was added dropwise DIPEA (0.88 mmol, 113 mg) followed by 3,5-dichlorobenzenesulfonyl chloride (0.922 mmol, 227 mg), a second equivalent of DIPEA and 4-DMAP (0.176 mmol, 22 mg). The reaction mixture was stirred at rt overnight when TLC (4:1 hexane:ethyl acetate) indicated disappearance of all starting material. The volatiles were removed in vacuo and the residue was purified by flash column chromatography on silica gel eluted with a gradient of hexane and ethyl acetate to yield N-(3,5-dichlorobenzenesulfonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, methyl ester (282 mg, 80%) as a white foam, homogeneous by TLC (Rf=0.55, 4:1 hexane:ethyl acetate);

Workup

  1. customThe volatiles were removed in vacuo
  2. customthe residue was purified by flash column chromatography on silica gel
  3. washeluted with a gradient of hexane and ethyl acetate

Sources & evidence

ORD record
ord-7c0bb575d6eb43eabbc16a8aa5b068dd
Source dataset
uspto-grants-2003_05
Patent number
US06559174B2

Reaction notes

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