1,2,3,4-Tetrahydroisoquinoline → 2-[2-(3-Thieno[2,3-d]isoxazol-3-yl-phenoxy)-ethyl]-1,2,3,4-tetrahydroisoquinoline

HRID 8666

Reaction equation

HRID 8666 reaction equation
Br[CH2:2][CH2:3][O:4][C:5]1[CH:6]=[C:7]([C:11]2[C:15]3[S:16][CH:17]=[CH:18][C:14]=3[O:13][N:12]=2)[CH:8]=[CH:9][CH:10]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH2:28][CH2:27][NH:26]1>C(#N)C>[O:13]1[C:14]2[CH:18]=[CH:17][S:16][C:15]=2[C:11]([C:7]2[CH:6]=[C:5]([CH:10]=[CH:9][CH:8]=2)[O:4][CH2:3][CH2:2][N:26]2[CH2:27][CH2:28][C:29]3[C:34](=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:25]2)=[N:12]1

Participants

5

Reactant 3

HCID 70461,2,3,4-TetrahydroisoquinolineHCID 11430Potassium CarbonateHCID 219835823-[3-(2-Bromo-ethoxy)-phenyl]-thieno[2,3-d]isoxazole

Product 1

HCID 99515982-[2-(3-Thieno[2,3-d]isoxazol-3-yl-phenoxy)-ethyl]-1,2,3,4-tetrahydroisoquinolineYield 61.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

Mix 3-[3-(2-bromo-ethoxy)-phenyl]-thieno[2,3-d]isoxazole (0.400 g, 1.23 mmol), potassium carbonate (0.345 g, 2.50 mmol), 1,2,3,4-tetrahydroisoquinoline (0.532 g, 3.99 mmol) and acetonitrile (5.0 mL) and heat at 75° C., overnight. Cool the reaction mixture and filter through a Waters Sep-Pak 1 g silica cartridge (ethyl acetate). Combine the appropriate fractions and concentrate to give a residue. Purify the residue by column (10 g silica) chromatography using a graded solvent mixture of 10% ethyl acetate in dichloromethane to 20% ethyl acetate in dichloromethane. Dissolve the free base in ethanol and acidify with ethereal hydrochloric acid, concentrate to a sticky residue, triturate (methanol:ethyl acetate) and collect the powder. Recrystallize the powder (methanol:ethyl acetate) to obtain the title compound as white crystals (0.285 g, 56%). mp=202–204° C. Microanalysis (C, H, N) is consistent with the final, desired compound.

Workup

  1. temperatureCool the reaction mixture
  2. filtrationfilter through a Waters Sep-Pak 1 g silica cartridge (ethyl acetate)
  3. concentrationCombine the appropriate fractions and concentrate
  4. customto give a residue
  5. customPurify the residue by column (10 g silica) chromatography
  6. additiona graded solvent mixture of 10% ethyl acetate in dichloromethane to 20% ethyl acetate in dichloromethane
  7. dissolutionDissolve the free base in ethanol
  8. concentrationconcentrate to a sticky residue
  9. customtriturate (methanol:ethyl acetate)
  10. customcollect the powder
  11. customRecrystallize the powder (methanol:ethyl acetate)

Sources & evidence

ORD record
ord-1574d05012d74272a3de0a8a27865291
Source dataset
uspto-grants-2006_08
Patent number
US07091199B1

Linked notes

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