Sulfuric Acid → Methyl 5-chloroisoquinolin-4-carboxylate

HRID 1470504Notes

Reaction equation

HRID 1470504 reaction equation
OS(O)(=O)=O.[CH:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([C:16]([O:18][CH3:19])=[O:17])=[CH:8][N:7]=1.C1C(=O)N([Cl:27])C(=O)C1>>[Cl:27][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:10]=1[C:9]([C:16]([O:18][CH3:19])=[O:17])=[CH:8][N:7]=[CH:6]2

Participants

4

Reactant 3

HCID 1118Sulfuric AcidHCID 31398ChlorosuccinimideHCID 11830161Methyl Isoquinoline-4-carboxylate

Product 1

HCID 68281881Methyl 5-chloroisoquinolin-4-carboxylateYield 77.7%

Conditions

Temperature
60 °C

Procedure

To a well stirred solution of conc. H2SO4 (28.5 mL) and methyl isoquinoline-4-carboxylate (5.0 g, 26.7 mmol) at 0° C. was added, NCS (35.7 g, 267 mmol) slowly and the reaction mixture was allowed to come to RT and then heated to 60° C. overnight. After completion (TLC), it was quenched with ice, neutralized (NaHCO3) and extracted with EtOAc (100 mL×3). The organic phase was separated, dried (Na2SO4) and concentrated to give dark brown oil (4.6 g) as crude product that was purified by flash column chromatography (15% EtOAc in Hexanes) to furnish the desired compound (3.8 g, 64%) as pale yellow oil.

Workup

  1. customto come to RT
  2. customAfter completion (TLC), it was quenched with ice
  3. extractionextracted with EtOAc (100 mL×3)
  4. customThe organic phase was separated
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-1ceab0309c0e4357837e2303c20f8670
Source dataset
uspto-grants-2015_04
Patent number
US09006442B2

Reaction notes

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