Water → 2-(3-Methoxypropoxy)-4-((R)-2-(bromomethyl)-3-methylbutyl)-1-methoxybenzene

HRID 1522950Notes

Reaction equation

HRID 1522950 reaction equation
[CH3:1][O:2][C:3]1[CH:15]=[CH:14][C:6]([CH2:7][C@H:8]([CH:11]([CH3:13])[CH3:12])[CH2:9]O)=[CH:5][C:4]=1[O:16][CH2:17][CH2:18][CH2:19][O:20][CH3:21].CN(C)C=O.P(Br)(Br)([Br:29])=O.O>CC1C=CC=CC=1.C(OCC)(=O)C.CCCCCC>[CH3:1][O:2][C:3]1[CH:15]=[CH:14][C:6]([CH2:7][C@H:8]([CH:11]([CH3:13])[CH3:12])[CH2:9][Br:29])=[CH:5][C:4]=1[O:16][CH2:17][CH2:18][CH2:19][O:20][CH3:21]

Participants

7

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 24613Phosphorus oxybromideHCID 9835828(R)-2-[3-(3-Methoxypropoxy)-4-methoxybenzyl]-3-methylbutan-1-OL

Product 1

HCID 113258232-(3-Methoxypropoxy)-4-((R)-2-(bromomethyl)-3-methylbutyl)-1-methoxybenzeneYield 75.1%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

Dissolve (R)-2-[4-methoxy-3-(3-methoxy-propoxy)-benzyl]-3-methyl butanol (14.82 g, 50 mmol) and N,N-dimethyl formamide (0.4 g, 5.5 mmol) in methyl benzene (234 ml), add phosphorus oxybromide (15.05 g, 52.5 mmol) in droplets slowly, and control the temperature below 60° C. in that process; then, let them to react at 80° C. for 2 hours; cool down to room temperature, add water (234 ml), stir for 20 minutes, and separate the layers; extract the aqueous layer with petroleum ether for three cycles, combine the organic layers and wash twice with saturated sodium bicarbonate and saturated sodium chloride respectively; dry the organic layer with anhydrous sodium sulfate, filter, and condense the filtrate so as to obtain 17.2 g of oily matter. Add mixed solvent of ethyl acetate/normal hexane (17.2 ml/34.4 ml), control the product to crystallize at −10° C., filter, and treat the filter cake by vacuum drying at room temperature, so as to obtain 13.5 g of white solid matter; the yield is 75.1%, mp: 51-53° C., chiral purity: ≧99.9%.

Workup

  1. customthe temperature below 60° C.
  2. customto react at 80° C. for 2 hours
  3. customseparate the layers
  4. extractionextract the aqueous layer with petroleum ether for three cycles
  5. washwash twice with saturated sodium bicarbonate and saturated sodium chloride respectively
  6. dry with materialdry the organic layer with anhydrous sodium sulfate
  7. filtrationfilter
  8. customcondense the filtrate so as
  9. customto obtain 17.2 g of oily matter
  10. additionAdd
  11. customto crystallize at −10° C.
  12. filtrationfilter
  13. additiontreat the filter cake by vacuum
  14. customdrying at room temperature

Sources & evidence

ORD record
ord-44fcf046e3af4df0bb63335283efe9a1
Source dataset
uspto-grants-2015_07
Patent number
US09079839B2

Reaction notes

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