Formaldehyde → 2-Hydroxy-5-methoxy-3-(2-phenylpropan-2-yl)benzaldehyde

HRID 1062523Notes

Reaction equation

HRID 1062523 reaction equation
C([Mg]Br)C.[C:5]([C:14]1[CH:19]=[C:18]([O:20][CH3:21])[CH:17]=[CH:16][C:15]=1[OH:22])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([CH3:7])[CH3:6].[CH2:23]=[O:24].C(N(CC)CC)C>C1COCC1.C1(C)C=CC=CC=1>[C:5]([C:14]1[CH:19]=[C:18]([O:20][CH3:21])[CH:17]=[C:16]([CH:23]=[O:24])[C:15]=1[OH:22])([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)([CH3:7])[CH3:6]

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 8471TriethylamineHCID 22281121HCID 22281121, compoundHCID 178418443HCID 178418443, compound

Product 1

HCID 222811182-Hydroxy-5-methoxy-3-(2-phenylpropan-2-yl)benzaldehydeYield 81%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
100 °C

Procedure

Into a 1 liter reactor thoroughly purged with nitrogen, 43.5 ml of an ether solution containing 130.7 mmol of ethylmagnesium bromide and 70 ml of THF were introduced. To the reactor, a solution containing 30.16 g (124.5 mmol) of 2-cumyl-4-methoxyphenol diluted with 80 ml of a THF was dropwise added at 0° C. over a period of 30 minutes. Then, 500 ml of toluene was added, and the system was heated to 100° C. to distill off about 40 ml of a mixed solution of ether and THF, whereby an opaque white slurry was obtained. After the slurry was cooled to 15° C., 9.04 g (301.3 mmol) of paraformaldehyde and 24.8 ml (178.0 mmol) of triethylamine were added, followed by stirring at 90° C. for 15 minutes. The reaction solution was allowed to cool to room temperature and then quenched with 84 ml of 18% hydrochloric acid. The organic layer was washed with 400 ml of water, 200 ml of a sodium hydrogencarbonate aqueous solution and a sodium chloride aqueous solution (200 ml×2), and then concentrated. The resulting liquid was purified by silica gel column chromatography to obtain 27.27 g (yield: 81%) of 3-cumyl-5-methoxysalicylaldehyde.

Workup

  1. customInto a 1 liter reactor thoroughly purged with nitrogen, 43.5 ml of an ether solution
  2. additionwere introduced
  3. additionwas dropwise added at 0° C. over a period of 30 minutes
  4. distillationto distill off about 40 ml of a mixed solution of ether and THF, whereby an opaque white slurry
  5. customwas obtained
  6. temperatureAfter the slurry was cooled to 15° C.
  7. temperatureto cool to room temperature
  8. customquenched with 84 ml of 18% hydrochloric acid
  9. washThe organic layer was washed with 400 ml of water, 200 ml of a sodium hydrogencarbonate aqueous solution
  10. concentrationa sodium chloride aqueous solution (200 ml×2), and then concentrated
  11. customThe resulting liquid was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-37a701ef742344fa849e99d5804a654d
Source dataset
uspto-grants-2005_11
Patent number
US06962890B2

Reaction notes

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