Dimethylformamide → 2-[(Benzyloxy)methyl]-6-bromo-2,3-dihydro-1,4-benzodioxine

HRID 965831Notes

Reaction equation

HRID 965831 reaction equation
[Br:1][C:2]1[CH:13]=[CH:12][C:5]2[O:6][CH:7]([CH2:10][OH:11])[CH2:8][O:9][C:4]=2[CH:3]=1.CN(C=O)C.[H-].[Na+].[CH2:21](Br)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>O>[CH2:21]([O:11][CH2:10][CH:7]1[O:6][C:5]2[CH:12]=[CH:13][C:2]([Br:1])=[CH:3][C:4]=2[O:9][CH2:8]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 233966(6-BROMO-2,3-DIHYDROBENZO[B][1,4]DIOXIN-2-YL)METHANOL

Product 1

HCID 223132912-[(Benzyloxy)methyl]-6-bromo-2,3-dihydro-1,4-benzodioxineYield 73%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of (6-bromo-2,3-dihydro-1,4-benzodioxin-2-yl)methanol (3.94 g, 16.1 mmol) and DMF (35 mL) at rt is treated with a 60% dispersion of NaH in mineral oil (0.706 g, 17.7 mmol). After 15 min, the mixture is treated with benzyl bromide (2.10 mL, 17.7 mmol). After 2 h, the mixture is poured into H2O and extracted with EtOAc (2×125 mL). The combined organics are washed with H2O (3×100 mL), brine, dried (MgSO4), filtered, and concentrated. The resulting oil is adsorbed onto SiO2 and chromatographed (Biotage 40M+SIM, 5% EtOAc/Hexane). The product fractions are pooled and concentrated to give an oil which solidified (upon standing) to give 3.91 g (73%) of 2-[(benzyloxy)methyl]-6-bromo-2,3-dihydro-1,4-benzodioxine: 1H NMR (400 MHz, CDCl3) δ 7.30-7.45, 7.06, 6.99, 6.81, 4.60-4.70, 4.30-4.40, 4.05-4.15, 3.65-3.85; MS (EI) m/z 244 (M+).

Workup

  1. waitAfter 2 h
  2. extractionextracted with EtOAc (2×125 mL)
  3. washThe combined organics are washed with H2O (3×100 mL), brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customchromatographed (Biotage 40M+SIM, 5% EtOAc/Hexane)
  8. concentrationconcentrated
  9. customto give an oil which

Sources & evidence

ORD record
ord-30aa51b6e7494f5590f013ff3deb0aa6
Source dataset
uspto-grants-2005_10
Patent number
US06951868B2

Reaction notes

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