Chlorotrimethylsilane → 1,2,3,4,-Tetrahydro-6-hydroxy-N-3-(2-thienyl)propionylisoquinoline

HRID 1088696Notes

Reaction equation

HRID 1088696 reaction equation
Br.[OH:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH2:9][NH:8][CH2:7][CH2:6]2.Cl[Si](C)(C)C.[S:18]1[CH:22]=[CH:21][CH:20]=[C:19]1[CH2:23][CH2:24][C:25](O)=[O:26].ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl.C1COCC1>[OH:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH2:9][N:8]([C:25](=[O:26])[CH2:24][CH2:23][C:19]1[S:18][CH:22]=[CH:21][CH:20]=1)[CH2:7][CH2:6]2

Participants

8

Reactant 5

HCID 6397ChlorotrimethylsilaneHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 7031693-(2-Thienyl)propanoic acidHCID 133617991,2,3,4-Tetrahydroisoquinolin-6-ol--hydrogen bromide (1/1)

Product 1

HCID 157187121,2,3,4,-Tetrahydro-6-hydroxy-N-3-(2-thienyl)propionylisoquinolineYield 63.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A suspension of 1,2,3,4-tetrahydro-6-hydroxyisoquinoline hydrobromide (5.8g) in methylene chloride (100 mL) at 0° C. was treated with chlorotrimethylsilane (7.4 mL). After 4 hours, the reaction was filtered, washed with cold NaHCO3, brine, dried (MgSO4), filtered and evaporated to provide an oil. To a solution of the above oil in THF (100 mL), was added 3-(2-thienyl)propanoic acid (4.33 g) and 1-hydroxybenzotriazole (6.8 g) followed by the addition of dicyclohexylcarbodiimide (5.2 g). After 12 hours, the reaction was filtered and concentrated. The residue was taken up into EtOAc and refiltered. The organic solution was washed with 10% aq. NaHCO3, 1 N HCl, brine, dried (MgSO4), filtered and concentrated. Chromatography on silica gel (elution with 50% ethyl acetate/hexanes) provided 4.61 g of the desired product as a white solid.

Workup

  1. filtrationthe reaction was filtered
  2. washwashed with cold NaHCO3, brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customevaporated
  6. customto provide an oil
  7. waitAfter 12 hours
  8. filtrationthe reaction was filtered
  9. concentrationconcentrated
  10. washThe organic solution was washed with 10% aq. NaHCO3, 1 N HCl, brine
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-653d059b33e44615bc22274a23cb6234
Source dataset
uspto-grants-1990_10
Patent number
US04963563

Reaction notes

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