Trifluoroacetic acid → 2-(6,7-Dimethoxy-3,4-dihydro-1H-isoquinoline-2-sulfonylmethyl)-3-methyl-butyric Acid

HRID 585496Notes

Reaction equation

HRID 585496 reaction equation
C([O:5][C:6](=[O:16])[CH:7]([CH2:11][S:12](Cl)(=[O:14])=[O:13])[CH:8]([CH3:10])[CH3:9])(C)(C)C.Cl.[CH3:18][O:19][C:20]1[CH:21]=[C:22]2[C:27](=[CH:28][C:29]=1[O:30][CH3:31])[CH2:26][NH:25][CH2:24][CH2:23]2.C(N(CC)CC)C.FC(F)(F)C(O)=O>ClCCl.CCCCCC>[CH3:18][O:19][C:20]1[CH:21]=[C:22]2[C:27](=[CH:28][C:29]=1[O:30][CH3:31])[CH2:26][N:25]([S:12]([CH2:11][CH:7]([CH:8]([CH3:9])[CH3:10])[C:6]([OH:5])=[O:16])(=[O:13])=[O:14])[CH2:24][CH2:23]2

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 64560356,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochlorideHCID 212590942-Chlorosulfonylmethyl-3-methyl-butyric acid tert-butyl ester

Product 1

HCID 101772382-(6,7-Dimethoxy-3,4-dihydro-1H-isoquinoline-2-sulfonylmethyl)-3-methyl-butyric AcidYield 25%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8058HexaneSolvent

Procedure

2-Chlorosulfonylmethyl-3-methyl-butyric acid tert-butyl ester (1.0 ml of a 1M solution in dichloromethane) was added to a solution of 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (230 mg) and triethylamine (0.31 ml) in dichloromethane (10 ml) and the mixture stirred at room temperature for 16 h. Trifluoroacetic acid was added (5 ml) and the reaction left to stir for 2 h then diluted with hexane (10 ml) and evaporated under reduced pressure. The residue was azeotroped with 1:1 dichloromethane-hexane (2×10 ml), dissolved in 1M sodium hydroxide and washed with diethyl ether (2×10 ml) The aqueous was acidified to pH=4 with citric acid and extracted with ethyl acetate (2×15 ml). The combined extracts were washed with water (10 ml) and brine (10 ml), dried (Na2SO4), filtered and evaporated under reduced pressure to give the title compound (93 mg, 25%).

Workup

  1. waitthe reaction left
  2. stirringto stir for 2 h
  3. customevaporated under reduced pressure
  4. customThe residue was azeotroped with 1:1 dichloromethane-hexane (2×10 ml)
  5. dissolutiondissolved in 1M sodium hydroxide
  6. washwashed with diethyl ether (2×10 ml) The
  7. extractionextracted with ethyl acetate (2×15 ml)
  8. washThe combined extracts were washed with water (10 ml) and brine (10 ml)
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-585ce26746234207a13739d885a297f4
Source dataset
uspto-grants-2005_08
Patent number
US06933306B2

Reaction notes

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