Potassium Acetate → (2-(Tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinolin-6-YL)boronic acid pinacol ester

HRID 1712946Notes

Reaction equation

HRID 1712946 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH2:8][N:7]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:6][CH2:5]2.Br[C:20]1[CH:21]=[CH:22][CH:23]=[C:24]2[C:29]=1[CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]2.[B:37]1([B:46]2[O:50][C:49]([CH3:52])([CH3:51])[C:48]([CH3:54])([CH3:53])[O:47]2)[O:41][C:40]([CH3:43])([CH3:42])[C:39]([CH3:45])([CH3:44])[O:38]1.C([O-])(=O)C.[K+]>CN(C=O)C.CCOC(C)=O>[CH3:44][C:39]1([CH3:45])[C:40]([CH3:43])([CH3:42])[O:41][B:37]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[CH2:8][N:7]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:6][CH2:5]3)[O:38]1.[CH3:52][C:49]1([CH3:51])[C:48]([CH3:53])([CH3:54])[O:47][B:46]([C:20]2[CH:21]=[CH:22][CH:23]=[C:24]3[C:29]=2[CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]3)[O:50]1

Participants

8

Reactant 4

HCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 49761184tert-Butyl 6-bromo-3,4-dihydroisoquinoline-2(1H)-carboxylateHCID 59463272Tert-butyl 8-bromo-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

Product 2

HCID 52987621(2-(Tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinolin-6-YL)boronic acid pinacol esterHCID 66734880tert-butyl 8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

A solution of tert-butyl 6-bromo-3,4-dihydroisoquinoline-2(1H)-carboxylate and tert-butyl 8-bromo-3,4-dihydroisoquinoline-2(1H)-carboxylate (19.5 mmol), bis(pinacolato)diboron (21.4 mmol) and potassium acetate (61 mmol) in DMF (100 mL) was degassed. To this solution was added PdCl2dppf (1:1 complex with DCM, 0.8 mmol). The reaction mixture was heated at 85° C. for 4 hr and then allowed to cool to room temperature and diluted with EtOAc. The solution was washed with water and brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to give tert-butyl 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate and tert-butyl 8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylate. LCMS: (FA) ES+ 360 (for each).

Workup

  1. temperatureto cool to room temperature
  2. washThe solution was washed with water and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-a55c4fd544d148ee9c20db86cc77cc94
Source dataset
uspto-grants-2010_09
Patent number
US07795249B2

Reaction notes

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