Hydrochloric Acid → 7-Nitro-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid methyl ester hydrochloride

HRID 369974Notes

Reaction equation

HRID 369974 reaction equation
S(=O)(=O)(O)O.[ClH:6].[CH2:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:10][CH:9]([C:17]([OH:19])=[O:18])[NH:8]1.Cl.[N+:21]([O-:24])([O-])=[O:22].[K+].O.O.O.[C:29]([O-])(=O)C.[Na+]>O>[ClH:6].[CH3:29][O:18][C:17]([CH:9]1[CH2:10][C:11]2[C:16](=[CH:15][C:14]([N+:21]([O-:24])=[O:22])=[CH:13][CH:12]=2)[CH2:7][NH:8]1)=[O:19]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 1118Sulfuric AcidHCID 24434Potassium NitrateHCID 27241351,2,3,4-Tetrahydroisoquinoline-3-carboxylic acid hydrochlorideHCID 23665404Sodium Acetate Trihydrate

Product 1

HCID 672713487-Nitro-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid methyl ester hydrochlorideYield 49.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
3 °C

Procedure

To concentrated sulfuric acid (200 ml), cooled in an ice bath, was added portionwise 1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid hydrochloride (20.4 g, 95.5 mmol). The mixture was stirred, with continued cooling, until the evolution of hydrogen chloride gas ceased. Then, potassium nitrate (9.8 g, 96.9 mmol) was added, in portions, whilst maintaining the temperature under 3° C. The mixture was stirred overnight, allowing it to come to room temperature, and then poured onto ice. Sodium acetate trihydrate (1.02 kg), dissolved in water, was then added to the resulting solution. Sufficient water was added to solubilize the salts; the final reaction volume was 5 l. The product was filtered off, washed with water and air dried, yield 17.35 g. NMR indicated this to be a mixture of the 7-nitro isomer (major component) and the 6-nitro isomer (minor component). This mixture was added to methanol (210 ml), the mixture acidified with dry hydrogen chloride, refluxed for 4 h and then allowed to cool with stirring. The product was filtered off, washed with methanol and air dried to yield 7-nitro-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid methyl ester hydrochloride (12.9 g), pure by NMR. The hydrochloride salt was dissolved in water and the solution basified with concentrated ammonium hydroxide and stirred for 0.5 h. The solid was filtered off, washed with water and air dried to yield 7-nitro-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid methyl ester (9.97 g), m.p. 133-5° C.

Workup

  1. customto come to room temperature
  2. additionpoured onto ice
  3. additionwas then added to the resulting solution
  4. customthe final reaction volume
  5. filtrationThe product was filtered off
  6. washwashed with water and air
  7. customdried
  8. additiona mixture of the 7-nitro isomer (major component)
  9. additionThis mixture was added to methanol (210 ml)
  10. temperaturerefluxed for 4 h
  11. temperatureto cool
  12. stirringwith stirring
  13. filtrationThe product was filtered off
  14. washwashed with methanol and air
  15. customdried

Sources & evidence

ORD record
ord-4a8df6cd0275416e90155ba45e178184
Source dataset
uspto-grants-2000_10
Patent number
US06140322

Reaction notes

Loading…