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

HRID 63286Notes

Reaction equation

HRID 63286 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-9bcdb4c136de418499bfd01f728217b5
Source dataset
uspto-grants-2016_09
Patent number
US09447074B2

Reaction notes

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