Triethylamine → 5-Chloromethyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

HRID 586722Notes

Reaction equation

HRID 586722 reaction equation
C(N(CC)CC)C.CS([Cl:12])(=O)=O.[C:13]([O:17][C:18]([N:20]1[CH2:29][CH2:28][C:27]2[C:22](=[CH:23][CH:24]=[CH:25][C:26]=2[CH2:30]O)[CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14]>O1CCCC1.[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C>[C:13]([O:17][C:18]([N:20]1[CH2:29][CH2:28][C:27]2[C:22](=[CH:23][CH:24]=[CH:25][C:26]=2[CH2:30][Cl:12])[CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 695612161,1-Dimethylethyl 3,4-dihydro-5-(hydroxymethyl)-2(1H)-isoquinolinecarboxylate

Product 1

HCID 208259525-Chloromethyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl esterYield 46.1%

Reagents, catalysts & solvents 3

HCID 70681Tetrabutylammonium ChlorideCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Triethylamine (160 μl, 1,16 mmol) and then methane sulphonyl chloride (72 μl, 0.92 mmol) were added to 5-hydroxymethyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (202 mg, 0.77 mmol) (WO 02053558 p 59) in tetrahydrofuran (20 ml) and the mixture was stirred for 30 minutes. Tetrabutyl ammonium chloride (322 mg, 1.16 mmol) was added and the mixture was stirred for 2 hours at room temperature. The reaction mixture was diluted with ethyl acetate and the organic solution was washed with sodium hydrogen carbonate solution, dried over magnesium sulphate and evaporated under reduced pressure. The residue was purified by chromatography on silica gel using methanol in dichloromethane as eluant (2:98) to give the title compound (100 mg).

Workup

  1. stirringthe mixture was stirred for 2 hours at room temperature
  2. washthe organic solution was washed with sodium hydrogen carbonate solution
  3. dry with materialdried over magnesium sulphate
  4. customevaporated under reduced pressure
  5. customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-0241f1bcbd68456c8e438f2705742e10
Source dataset
uspto-grants-2005_08
Patent number
US06936619B2

Reaction notes

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