Sodium Hydroxide → Benzyl 7-amino-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 1524293Notes

Reaction equation

HRID 1524293 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][C:15]([N+:21]([O-])=O)=[CH:16][CH:17]=2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Sn](Cl)Cl.O.O.[Sn](Cl)Cl.[OH-].[Na+]>C(O)(=O)C.Cl.O.CCOC(C)=O>[CH2:1]([O:8][C:9]([N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][C:15]([NH2:21])=[CH:16][CH:17]=2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 14798Sodium Hydroxide2×HCID 24479Stannous ChlorideHCID 61436Stannous chloride dihydrate2×HCID 53419203Benzyl 7-nitro-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

Product 1

HCID 53419255Benzyl 7-amino-3,4-dihydroisoquinoline-2(1H)-carboxylateYield 111.9%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 313Hydrochloric AcidSolvent2×HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 7-nitro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (14.70 g, 42.36 mmol) in glacial acetic acid (180 mL), add a solution of tin(II) chloride (25.0 g, 129.21 mmol) and tin(II) chloride dihydrate (19.5 g, 84.72 mmol) as a solution in 10% HCl (71 mL). Stir the resulting solution at room temperature for 24 h. TLC indicates an incomplete reaction. Add more tin(II) chloride dihydrate (49.3 g, 213.95 mmol) followed by 6M HCl (20 mL) and stir the reaction 24 h more at room temperature. TLC now shows complete reaction. Pour the reaction into a vigorously stirring solution of NaOH (135.4 g) in water (250 mL) with ice (500 mL) and EtOAc (600 mL). Stir the suspension vigorously for 10 min (pH=5) then add more NaOH (72 g) as a solution in water (100 mL). The suspension clears up on vigorous stifling for 1 h. Partition the layers (pH aq=9-10) and extract the aqueous with more EtOAc (2×600 mL). Dry the combined organics (K2CO3 and Na2SO4) and concentrate in vacuo. Dissolve the residue in methylene chloride and filter to remove residual inorganics. Remove the solvent in vacuo to give 13.38 g of 7-amino-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester as an oil.

Workup

  1. customan incomplete reaction
  2. stirringstir
  3. customthe reaction 24 h more at room temperature
  4. customTLC now shows complete reaction
  5. additionPour
  6. stirringStir the suspension vigorously for 10 min (pH=5)
  7. waitThe suspension clears up on vigorous stifling for 1 h
  8. customPartition the layers (pH aq=9-10)
  9. extractionextract the aqueous with more EtOAc (2×600 mL)
  10. dry with materialDry the combined organics (K2CO3 and Na2SO4)
  11. concentrationconcentrate in vacuo
  12. dissolutionDissolve the residue in methylene chloride
  13. filtrationfilter
  14. customto remove residual inorganics
  15. customRemove the solvent in vacuo

Sources & evidence

ORD record
ord-03f2dc3fd2744147a608180c0ee2fb5d
Source dataset
uspto-grants-2015_07
Patent number
US09079880B2

Reaction notes

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