Water → 4,4,5,5-Tetramethyl-2-[3-((R)-2,2,2-trifluoro-1-methylethoxymethyl)phenyl)-[1,3,2]dioxaborolane

HRID 83561Notes

Reaction equation

HRID 83561 reaction equation
[F:1][C:2]([F:7])([F:6])[C@H:3]([OH:5])[CH3:4].[H-].[Na+].Br[CH2:11][C:12]1[CH:13]=[C:14]([B:18]2[O:22][C:21]([CH3:24])([CH3:23])[C:20]([CH3:26])([CH3:25])[O:19]2)[CH:15]=[CH:16][CH:17]=1.O>CN(C)C=O>[CH3:23][C:21]1([CH3:24])[C:20]([CH3:25])([CH3:26])[O:19][B:18]([C:14]2[CH:15]=[CH:16][CH:17]=[C:12]([CH2:11][O:5][C@H:3]([CH3:4])[C:2]([F:7])([F:6])[F:1])[CH:13]=2)[O:22]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 27732832-[3-(Bromomethyl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 6993809(2R)-1,1,1-trifluoropropan-2-ol

Product 1

HCID 712879074,4,5,5-Tetramethyl-2-[3-((R)-2,2,2-trifluoro-1-methylethoxymethyl)phenyl)-[1,3,2]dioxaborolaneYield 71.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Under argon stream, to a solution of (R)-1,1,1-trifluoropropan-2-ol (3.32 g) in N,N-dimethylformamide (43 ml) was added portionwise sodium hydride (1.16 g, 60 wt % oil dispersion) at 0° C., and the mixture was stirred for 20 minutes. Then, 2-(3-bromomethylphenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (4.32 g) was added thereto, and then the mixture was stirred at room temperature overnight. To this reaction mixture were sequentially added water and a 2M aqueous solution of hydrochloric acid, and the mixture was extracted with ethyl acetate. This organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=1/0 to 19/1) to give the titled compound (3.43 g).

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. extractiona 2M aqueous solution of hydrochloric acid, and the mixture was extracted with ethyl acetate
  3. washThis organic layer was washed with a saturated aqueous solution of sodium chloride
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=1/0 to 19/1)

Sources & evidence

ORD record
ord-375cf582958241e9b9e0007ee696208f
Source dataset
uspto-grants-2014_09
Patent number
US08846746B2

Reaction notes

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