8-Bromoisoquinoline → Tert-butyl 2-(isoquinolin-8-yl)acetate

HRID 1519748Notes

Reaction equation

HRID 1519748 reaction equation
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[CH:10]=[N:9][CH:8]=[CH:7]2.[Br-].[C:13]([O:17][C:18](=[O:21])[CH2:19][Zn+])([CH3:16])([CH3:15])[CH3:14]>C1COCC1.CC(P(C(C)(C)C)[C-]1C=CC=C1)(C)C.C1C=CC([C-]2C(C3C=CC=CC=3)=C(C3C=CC=CC=3)C(C3C=CC=CC=3)=C2C2C=CC=CC=2)=CC=1.[Fe+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[CH:10]1[C:11]2[C:6](=[CH:5][CH:4]=[CH:3][C:2]=2[CH2:19][C:18]([O:17][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:21])[CH:7]=[CH:8][N:9]=1

Participants

6

Reactant 2

HCID 98591348-BromoisoquinolineHCID 178451181HCID 178451181, compound

Product 1

HCID 68757728Tert-butyl 2-(isoquinolin-8-yl)acetateYield 78%

Reagents, catalysts & solvents 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 129828017Ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane;iron(2+);(2,3,4,5-tetraphenylcyclopenta-1,4-dien-1-yl)benzeneCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a suspension of 8-bromoisoquinoline (2.0 g, 9.7 mmol), Q-phos (68 mg, 0.096 mmol) and Pd(dba)2 (132 mg, 0.14 mmol) in dry THF (30 mL) was added 40 mL of (2-tert-butoxy-2-oxoethyl)zinc(II) bromide solution under N2 protection. The resulting mixture was heated at 80° C. overnight. The solvent was evaporated under vacuum and the crude residue was diluted with ethyl acetate (100 mL) and washed with water (3×50 mL). The combined organic layer was washed with brine, dried over Na2SO4 and the solvent was evaporated under vacuum to give a residue which was purified with silica gel chromatography to give tert-butyl 2-(isoquinolin-8-yl)acetate (1.85 g, 78%).

Workup

  1. customThe solvent was evaporated under vacuum
  2. additionthe crude residue was diluted with ethyl acetate (100 mL)
  3. washwashed with water (3×50 mL)
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. customthe solvent was evaporated under vacuum
  7. customto give a residue which
  8. customwas purified with silica gel chromatography

Sources & evidence

ORD record
ord-66ccbe8b19ba44038aae102d5b2437aa
Source dataset
uspto-grants-2015_07
Patent number
US09073891B2

Reaction notes

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