Hydrochloric Acid → 7-(5-Fluoro-2-{[(4-methyl-2-pyridinyl)methyl]oxy}phenyl)-1,2,3,4-tetrahydroisoquinoline

HRID 880006Notes

Reaction equation

HRID 880006 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH2:26][C:27]2[CH:32]=[C:31]([CH3:33])[CH:30]=[CH:29][N:28]=2)=[C:6]([C:8]2[CH:17]=[C:16]3[C:11]([CH2:12][CH2:13][N:14](C(OC(C)(C)C)=O)[CH2:15]3)=[CH:10][CH:9]=2)[CH:7]=1.Cl.C(OCC)(=O)C.[OH-].[Na+]>O1CCOCC1.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][CH2:26][C:27]2[CH:32]=[C:31]([CH3:33])[CH:30]=[CH:29][N:28]=2)=[C:6]([C:8]2[CH:17]=[C:16]3[C:11]([CH2:12][CH2:13][NH:14][CH2:15]3)=[CH:10][CH:9]=2)[CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 706649621,1-dimethylethyl 7-(5-fluoro-2-{[(4-methyl-2-pyridinyl)methyl]oxy}phenyl)-3,4-dihydro-2(1H)-isoquinolinecarboxylate

Product 1

HCID 706652897-(5-Fluoro-2-{[(4-methyl-2-pyridinyl)methyl]oxy}phenyl)-1,2,3,4-tetrahydroisoquinoline

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Procedure

1,1-Dimethylethyl 7-(5-fluoro-2-{[(4-methyl-2-pyridinyl)methyl]oxy}phenyl)-3,4-dihydro-2(1H)-isoquinolinecarboxylate (0.169 g) was dissolved in dioxane (1 ml). This was ice cooled before adding dropwise a solution of hydrogen chloride in dioxane (2 ml). This was stirred at room temperature overnight before concentrating in vacuo. The residue obtained was dissolved in water and backwashed with ethyl acetate. The aqueous layer was neutralised with aqueous sodium hydroxide (1M) and extracted with ethyl acetate. The organics were concentrated in vacuo and purified by preparative HPLC. Appropriate fractions were concentrated, neutralised with aqueous sodium bicarbonate and extracted with ethyl acetate. The organics were concentrated in vacuo to yield the title compound, 0.061 g (47%).

Workup

  1. concentrationbefore concentrating in vacuo
  2. customThe residue obtained
  3. extractionextracted with ethyl acetate
  4. concentrationThe organics were concentrated in vacuo
  5. custompurified by preparative HPLC
  6. concentrationAppropriate fractions were concentrated
  7. extractionextracted with ethyl acetate
  8. concentrationThe organics were concentrated in vacuo

Sources & evidence

ORD record
ord-e1a254636021429ea4a35f0278206dd3
Source dataset
uspto-grants-2015_03
Patent number
US08993560B2

Reaction notes

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