Methanol → HCID 53419788, compound

HRID 2423403Notes

Reaction equation

HRID 2423403 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH:7]([C:12]([OH:14])=[O:13])[NH:8][CH2:9]2)=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[CH3:19]O>>[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:12]([O:14][CH3:19])=[O:13])[N:8]=[CH:9]2)=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 887MethanolHCID 24386Thionyl ChlorideHCID 44295377-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic Acid

Product 1

HCID 53419788HCID 53419788, compoundYield 46%

Procedure

To a solution of 4.36 g (22.6 mmol) of 7-hydroxy-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid in 100 mL of MeOH was added 4.95 mL (67.7 mmol) of thionyl chloride and the solution was refluxed for 1 hr. After evaporation of the solvent, the residue was stirred vigorously in a mixture of 200 mL of EtOAc, 500 mL of H2O and 100 mL of saturated Na2CO3 (aq) until all solids dissolved. The aqueous layer was then saturated with sodium chloride and extracted twice with EtOAc. The combined organics were then washed with brine, dried over Na2SO4 and concentrated to a solid. To this solid was added 200 mL of xylenes and 3.0 g of palladium on carbon (10%) and the suspension was refluxed for 16 hr. The suspension was filtered through a pad of Celite® and silica gel. The pad was then washed with 50 mL of xylenes. The filtrate was discarded and the filter cake washed with 500 mL of a 4:1 mixture of CH2Cl2:MeOH. This filtrate was then evaporated to give 2.09 g (46%) of methyl 7-hydroxy-3-isoquinolinecarboxylate as a light brown solid. 1H NMR (400 MHz, DMSO-d6): δ 10.58 (s, 1H), 9.08 (s, 1H), 8.49 (s, 1H), 8.04 (d, J=9 Hz, 1H), 7.39 (d, J=9 Hz, 1H), 7.36 (s, 1H), 3.87 (s, 3H). ESI-LCMS m/z 204 (M+H)+.

Workup

  1. temperaturethe solution was refluxed for 1 hr
  2. customAfter evaporation of the solvent
  3. dissolutiondissolved
  4. extractionsaturated with sodium chloride and extracted twice with EtOAc
  5. washThe combined organics were then washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to a solid
  8. additionTo this solid was added 200 mL of xylenes and 3.0 g of palladium on carbon (10%)
  9. temperaturethe suspension was refluxed for 16 hr
  10. filtrationThe suspension was filtered through a pad of Celite® and silica gel
  11. washThe pad was then washed with 50 mL of xylenes
  12. washthe filter cake washed with 500 mL of a 4:1 mixture of CH2Cl2
  13. customThis filtrate was then evaporated

Sources & evidence

ORD record
ord-86e32e9fb04c4c97ab24b390c7a48744
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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