Sodium hydride → 2-((Cyclopropylmethoxy)methyl)-2,3-dihydro-6-nitrobenzo[b][1,4]dioxine

HRID 970644Notes

Reaction equation

HRID 970644 reaction equation
[N+:1]([C:4]1[CH:15]=[CH:14][C:7]2[O:8][CH:9]([CH2:12][OH:13])[CH2:10][O:11][C:6]=2[CH:5]=1)([O-:3])=[O:2].[H-].[Na+].Cl[CH2:19][CH:20]1[CH2:22][CH2:21]1>CCCC[N+](CCCC)(CCCC)CCCC.[Br-].CN(C=O)C>[CH:20]1([CH2:19][O:13][CH2:12][CH:9]2[O:8][C:7]3[CH:14]=[CH:15][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][C:6]=3[O:11][CH2:10]2)[CH2:22][CH2:21]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 80013(Chloromethyl)cyclopropaneHCID 12736691(6-Nitro-2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methanol

Product 1

HCID 687021632-((Cyclopropylmethoxy)methyl)-2,3-dihydro-6-nitrobenzo[b][1,4]dioxineYield 62.2%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

(2,3-dihydro-6-nitrobenzo[b][1,4]dioxin-2-yl)methanol (500 mg, 0.002 mol) and sodium hydride (0.28 g, 0.0070 mol) were placed in a flask under nitrogen. The flask was placed in an ice bath and 25 mL DMF was added. The reaction was stirred at 0° C. for 10 minutes and then (chloromethyl)cyclopropane (440 μL, 0.0048 mol) was added. The mixture was warmed to room temp over 20 min then tetra-N-butylammonium bromide (1.53 g, 0.00475 mol) was added to the mixture and the reaction was stirred at room temperature overnight. The reaction was partitioned between EtOAc and water. The organic layer was separated, washed with brine, dried (Na2SO4), filtered and the filtrate was concentrated under vacuum to an oil. The oil was purified by column chromatography on silica gel using EtOAc/hexanes (10%) as eluent to give a yellow solid (0.33 g, 50%) as a solid. m/z=266 (M+1).

Workup

  1. customThe flask was placed in an ice bath
  2. temperatureThe mixture was warmed to room temp over 20 min
  3. stirringthe reaction was stirred at room temperature overnight
  4. customThe reaction was partitioned between EtOAc and water
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationthe filtrate was concentrated under vacuum to an oil
  10. customThe oil was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-d987016fd69549aea90ceb78da3dc8de
Source dataset
uspto-grants-2007_12
Patent number
US07312233B2

Reaction notes

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