Hydrochloric Acid → 4-[(1S)-1-[[(3R)-2-(2-(4-fluorophenoxy)ethyl)-3,4-dihydro-1H-isoquinoline-3-carbonyl]amino]ethyl]benzoic acid hydrochloride

HRID 2205309Notes

Reaction equation

HRID 2205309 reaction equation
[F:1][C:2]1[CH:35]=[CH:34][C:5]([O:6][CH2:7][CH2:8][N:9]2[C@@H:18]([C:19]([NH:21][C@H:22]([C:24]3[CH:33]=[CH:32][C:27]([C:28]([O:30]C)=[O:29])=[CH:26][CH:25]=3)[CH3:23])=[O:20])[CH2:17][C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH2:10]2)=[CH:4][CH:3]=1.[OH-].[Na+].[ClH:38].O1CCOCC1>CO.O1CCCC1>[ClH:38].[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][CH2:7][CH2:8][N:9]2[C@@H:18]([C:19]([NH:21][C@H:22]([C:24]3[CH:25]=[CH:26][C:27]([C:28]([OH:30])=[O:29])=[CH:32][CH:33]=3)[CH3:23])=[O:20])[CH2:17][C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH2:10]2)=[CH:34][CH:35]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 312751,4-DioxaneHCID 118876972methyl 4-[(1S)-1-[[(3R)-2-(2-(4-fluorophenoxy)ethyl)-3,4-dihydro-1H-isoquinoline-3-carbonyl]amino]ethyl]benzoate

Product 1

HCID 862806734-[(1S)-1-[[(3R)-2-(2-(4-fluorophenoxy)ethyl)-3,4-dihydro-1H-isoquinoline-3-carbonyl]amino]ethyl]benzoic acid hydrochlorideYield 93%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Dissolve methyl 4-[(1S)-1-[[(3R)-2-(2-(4-fluorophenoxy)ethyl)-3,4-dihydro-1H-isoquinoline-3-carbonyl]amino]ethyl]benzoate (550 mg, 1.15 mmol) in a mixture of methanol (10 mL) and tetrahydrofuran (10 mL). Add a 5 N aqueous solution of sodium hydroxide (0.462 mL, 2.31 mmol), then stir the mixture at room temperature overnight. Concentrate the mixture under reduced pressure to furnish a white solid. Add a 4 M solution of hydrogen chloride in 1,4-dioxane (10 mL, 40 mmol), and stir the mixture at room temperature for 10 min Remove the suspended solids by filtration, rinsing the solids with THF (5 mL). Concentrate the combine filtrate under reduced pressure to furnish a white solid. Triturate the material in hot diethyl ether (10 mL), and filter to furnish the title compound as a white solid (535 mg, 93% yield). Mass spectrum (m/z): 463 ([M+H]+), 485 ([M+Na]+).

Workup

  1. concentrationConcentrate the mixture under reduced pressure
  2. customto furnish a white solid
  3. stirringstir the mixture at room temperature for 10 min
  4. customRemove the suspended solids
  5. filtrationby filtration
  6. washrinsing the solids with THF (5 mL)
  7. concentrationConcentrate the combine filtrate under reduced pressure
  8. customto furnish a white solid
  9. customTriturate the material in hot diethyl ether (10 mL)
  10. filtrationfilter

Sources & evidence

ORD record
ord-b74afaf792bb4e34b3acec080c4986a3
Source dataset
uspto-grants-2016_06
Patent number
US09371289B2

Reaction notes

Loading…