Benzyl Bromide → HCID 86700886, compound

HRID 625083Notes

Reaction equation

HRID 625083 reaction equation
[OH:1][C:2]1[C:11]2[C:10](=[O:12])[O:9][C:8]([CH3:14])([CH3:13])[O:7][C:6]=2[CH:5]=[C:4]([O:15][CH3:16])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:23](Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>CN(C)C=O>[CH2:23]([O:1][C:2]1[C:11]2[C:10](=[O:12])[O:9][C:8]([CH3:13])([CH3:14])[O:7][C:6]=2[CH:5]=[C:4]([O:15][CH3:16])[CH:3]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 11424613HCID 11424613, compound

Product 1

HCID 86700886HCID 86700886, compoundYield 83.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-hydroxy-7-methoxy-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-one (30.00 g, 0.134 mol) in N,N-dimethylformamide (400 mL) was treated with powdered anhydrous potassium carbonate (19.41 g, 0.14 mol) added all at once. The resulting mixture was stirred in vacuo for 10 min. and then flushed with nitrogen. The reaction flask was placed in a water bath (22° C.) and treated with benzyl bromide (24.03 g, 0.14 mol) added dropwise over 15 min. The resulting mixture was then stirred at 22° C. for 18 h (no starting material left by tlc). The solid was filtered and washed with N,N-dimethylformamide. The filtrate was evaporated in vacuo and the residual oil was diluted with ethyl acetate (500 mL), washed with cold 0.1 N hydrochloric acid, saturated sodium bicarbonate and brine. After drying over anhydrous magnesium sulfate, evaporation of the solvent gave a thick syrup. Crystallization form ethyl acetate (50 mL) and hexane (150 mL) gave 35.17 g of 5-(benzyloxy)-7-methoxy-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-one as large colorless prisms. Chromatography of the mother liquors on silica gel (4×13 cm, elution toluene-ethyl acetate 0-5%) gave 6.64 g of additional material to afford a total yield of 41.81 g (99%). HRMS (ESI) calcd for C18H19O5 [M+H]+ m/z 315.1227, found 315.1386. 1H NMR (CDCl3, 600 MHz) δ 1.68 (s, 6H), 3.77 (s, 3H), 5.19 (s, 2H), 5.19 (s, 2H), 6.04 (d, J=2.03 Hz, 1H), 6.15 (d, J=2.03 Hz, 1H), 7.27 (broad t, 1H), 736 (broad t, 2H), 7.52 (broad d, 2H).

Workup

  1. additionadded all at once
  2. customflushed with nitrogen
  3. customThe reaction flask was placed in a water bath
  4. additionadded dropwise over 15 min
  5. stirringThe resulting mixture was then stirred at 22° C. for 18 h (no starting material
  6. waitleft by tlc)
  7. filtrationThe solid was filtered
  8. washwashed with N,N-dimethylformamide
  9. customThe filtrate was evaporated in vacuo
  10. additionthe residual oil was diluted with ethyl acetate (500 mL)
  11. washwashed with cold 0.1 N hydrochloric acid, saturated sodium bicarbonate and brine
  12. dry with materialAfter drying over anhydrous magnesium sulfate, evaporation of the solvent
  13. customgave a thick syrup
  14. customCrystallization form ethyl acetate (50 mL) and hexane (150 mL)

Sources & evidence

ORD record
ord-c707209aebff48d59c861cbfed2e209d
Source dataset
uspto-grants-2016_04
Patent number
US09303065B2

Reaction notes

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