Diethyl Ether → 2-Hydroxy-5-methyl-3-(2-phenylpropan-2-yl)benzaldehyde

HRID 229615Notes

Reaction equation

HRID 229615 reaction equation
C([Mg]Br)C.C[CH2:6][O:7]CC.[C:10]([C:19]1[CH:24]=[C:23]([CH3:25])[CH:22]=[CH:21][C:20]=1[OH:26])([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)([CH3:12])[CH3:11].C(N(CC)CC)C>C1(C)C=CC=CC=1.C1COCC1>[C:10]([C:19]1[CH:24]=[C:23]([CH3:25])[CH:22]=[C:21]([CH:6]=[O:7])[C:20]=1[OH:26])([C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)([CH3:12])[CH3:11]

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 8471TriethylamineHCID 948562-Cumyl-4-methylphenolHCID 178418443HCID 178418443, compound

Product 1

HCID 219514192-Hydroxy-5-methyl-3-(2-phenylpropan-2-yl)benzaldehydeYield 92%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Ethylmagnesium bromide 21.0 ml (an ether solution, 3.0N, 63.1 mmol) and THF 40 ml were charged in a 500 ml reactor purged with nitrogen, 20 ml of a THF solution containing 2-cumyl-4-methylphenol 13.61 g (60.1 mmol) was added dropwise to the reactor at 0° C. in 1 hour and after that, the temperature was gradually raised to a room temperature and the resultant mixture was stirred for 30 minutes at a room temperature, in which toluene 220 ml was added, and then heated to 100° C. and about 50 ml of the mixed solvents of ether and THF were evaporated off to obtain a slightly opaque slurry. After the slurry was cooled to 24° C., p-formaldehyde 4.37 g (145.5 mmol) and triethylamine 12.0 ml (86.0 mmol) were added and the resultant mixture was stirred at 90° C. for 1 hour. After being cooled to a room temperature, the mixture was quenched with 42 ml of 18% hydrochloric acid and an organic layer was concentrated and the obtained liquid was purified by silica gel column chromatography to obtain 3-cumyl-5-methylsalicylaldehyde 14.13 g (yield 92%).

Workup

  1. custompurged with nitrogen, 20 ml of a THF solution
  2. additionwas added dropwise to the reactor at 0° C. in 1 hour
  3. additionwas added
  4. temperatureheated to 100° C.
  5. customabout 50 ml of the mixed solvents of ether and THF were evaporated off
  6. customto obtain a slightly opaque slurry
  7. temperatureAfter the slurry was cooled to 24° C.
  8. temperatureAfter being cooled to a room temperature
  9. customthe mixture was quenched with 42 ml of 18% hydrochloric acid
  10. concentrationan organic layer was concentrated
  11. customthe obtained liquid was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-6f2317357e1f4227ad4fc5424b449ef5
Source dataset
uspto-grants-2009_07
Patent number
US07563849B2

Reaction notes

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