N-Methoxy-N-methylacetamide → 1-(2,2-Dimethyl-2,4-dihydro-1,3-benzodioxin-6-yl)ethan-1-one

HRID 490992

Reaction equation

HRID 490992 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[O:10][C:9]([CH3:12])([CH3:11])[O:8][CH2:7][C:6]=2[CH:13]=1.C([Li])CCC.CN(OC)[C:21](=[O:23])[CH3:22]>C1COCC1.C(OCC)(=O)C>[C:21]([C:2]1[CH:3]=[CH:4][C:5]2[O:10][C:9]([CH3:12])([CH3:11])[O:8][CH2:7][C:6]=2[CH:13]=1)(=[O:23])[CH3:22]

Participants

6

Reactant 3

HCID 537505N-Methoxy-N-methylacetamideHCID 145203386-Bromo-2,2-dimethyl-4H-benzo[d][1,3]dioxineHCID 178418339Butyllithium

Product 1

HCID 218806101-(2,2-Dimethyl-2,4-dihydro-1,3-benzodioxin-6-yl)ethan-1-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the product of step (a) (110 g, 0.46 mol) in 1.0 L of THF at −78° C. was added 236 mL (0.51 mol) of 2.14 M n-butyllithium in hexanes via a dropping funnel. After 30 minutes, N-methyl-N-methoxy acetamide (71 g, 0.69 mol, available from TCI) was added. After 2 hours, the reaction mixture was quenched with water, diluted with 2.0 L of 1.0 M aqueous phosphate buffer (pH=7.0) and extracted once with diethyl ether. The diethyl ether phase was washed once with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to give a light orange oil. The oil was dissolved in a minimum volume of ethyl acetate, diluted with hexanes, and to give the title compound as a crystalline solid.

Workup

  1. waitAfter 2 hours
  2. customthe reaction mixture was quenched with water
  3. additiondiluted with 2.0 L of 1.0 M aqueous phosphate buffer (pH=7.0)
  4. extractionextracted once with diethyl ether
  5. washThe diethyl ether phase was washed once with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give a light orange oil

Sources & evidence

ORD record
ord-4a2edf8a96af45adb0600e1fa74cbeb1
Source dataset
uspto-grants-2009_05
Patent number
US07528253B2

Linked notes

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