Methyl iodide → 2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinolin-1(2H)-one

HRID 1778662Notes

Reaction equation

HRID 1778662 reaction equation
[H-].[Na+].[CH3:3][C:4]1([CH3:22])[C:8]([CH3:10])([CH3:9])[O:7][B:6]([C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][CH:20]=2)[C:17](=[O:21])[NH:16][CH2:15][CH2:14]3)[O:5]1.[CH3:23]I>CN(C=O)C.C(OCC)(=O)C>[CH3:23][N:16]1[CH2:15][CH2:14][C:13]2[C:18](=[CH:19][CH:20]=[C:11]([B:6]3[O:5][C:4]([CH3:22])([CH3:3])[C:8]([CH3:9])([CH3:10])[O:7]3)[CH:12]=2)[C:17]1=[O:21]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 219556776-(Tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroisoquinolin-1-one

Product 1

HCID 576129762-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinolin-1(2H)-oneYield 36.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Sodium hydride (29.3 mg, 0.732 mmol) was added to a solution of 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinolin-1(2H)-one (100 mg, 0.366 mmol) in DMF (1.0 mL). The mixture was stirred at r.t. for 5 min, and then methyl iodide (57.0 μL, 0.915 mmol) was added. The mixture was stirred at 50° C. for 6 h, then diluted with ethyl acetate, and washed with water and brine. The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (gradient: 0-50%) to afford the desired product (0.038 g, 36%). LCMS (M+H)+=274.2.

Workup

  1. stirringThe mixture was stirred at 50° C. for 6 h
  2. washwashed with water and brine
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (gradient: 0-50%)

Sources & evidence

ORD record
ord-deec7a07d23a4d7287515b17ffa8dae7
Source dataset
uspto-grants-2016_02
Patent number
US09266892B2

Reaction notes

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