2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane → 3-Methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile

HRID 1473406Notes

Reaction equation

HRID 1473406 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[O:10][CH3:11].C([Li])CCC.C(O[B:21]1[O:25][C:24]([CH3:27])([CH3:26])[C:23]([CH3:29])([CH3:28])[O:22]1)(C)C>C(OCC)C>[CH3:11][O:10][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:2]=1[B:21]1[O:25][C:24]([CH3:27])([CH3:26])[C:23]([CH3:29])([CH3:28])[O:22]1)[C:6]#[N:7]

Participants

5

Reactant 3

HCID 50177412-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 225911814-Bromo-3-methoxybenzonitrileHCID 178418339Butyllithium

Product 1

HCID 689291003-Methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrileYield 53%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

A solution of 4-bromo-3-methoxybenzonitrile (Combi-Blocks, San Diego, Calif., 2.500 g, 11.79 mmol) in 100 mL of diethyl ether was cooled to −78° C. and was treated with n-butyllithium (4.95 ml, 12.38 mmol). After stirring for 10 minutes, 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3.07 ml, 16.51 mmol) was added, and the cooling bath was removed. After stirring for an additional 2 hours, LC/MS showed mostly product, so the reaction mixture was quenched with saturated NH4Cl solution. After stirring for 20 minutes, the reaction mixture was poured into a separatory funnel charged with EtOAc. The organic layer was separated, dried over MgSO4 and concentrated. Purification of the crude residue by silica gel column chromatography (0 to 100% EtOAc/heptane) gave 3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (1.62 g, 6.25 mmol, 53.0% yield) with minor impurities. m/z (ESI) 260.1 (M+H)+

Workup

  1. customthe cooling bath was removed
  2. stirringAfter stirring for an additional 2 hours
  3. customso the reaction mixture was quenched with saturated NH4Cl solution
  4. stirringAfter stirring for 20 minutes
  5. additionthe reaction mixture was poured into a separatory funnel
  6. additioncharged with EtOAc
  7. customThe organic layer was separated
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. customPurification of the crude residue by silica gel column chromatography (0 to 100% EtOAc/heptane)

Sources & evidence

ORD record
ord-f8b5c0a46a6a49678dee752a53075be4
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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