Dimethylformamide → 4-Methoxy-2,6-dimethylbenzaldehyde

HRID 1872421Notes

Reaction equation

Br[C:2]1[C:7]([CH3:8])=[CH:6][C:5]([O:9][CH3:10])=[CH:4][C:3]=1[CH3:11].C([Li])(C)(C)C.CN([CH:20]=[O:21])C>C1COCC1.CCOCC>[CH3:11][C:3]1[CH:4]=[C:5]([O:9][CH3:10])[CH:6]=[C:7]([CH3:8])[C:2]=1[CH:20]=[O:21]

Participants

Conditions

Temperature: -78 °C

Procedure

To 4-bromo-3,5-dimethylanisole (a compound of Formula 5 from Example 3) (20 g, 93.0 mmol) in 500 mL of THF at -78° C. was added 120 mL of tert-Butyllithium (1.7 M in pentane). The reaction mixture was stirred for 30 minutes at -78° C. and then DMF (136.0 g, 186.0 mmol) was added. The reaction mixture was stirred for 1 hour at -78° C. and for 1.5 hours at room temperature, diluted with 300 mL of ether, washed with 300 mL of water, acidified 1N HC1, and 5×100 mL of brine. The organic portion was dried (MgSO4), filtered, and evaporated to give the crude product, which was purified by flash column chromatography (silica gel, 90:10 hexane/ethylacetate) to yield 2,6-dimethyl-4-methoxybenzaldehyde (a compound of Formula 6), (9.50 g, 57.8 mmol, 62%) as a white solid; 1HNMR (CDCl3 δ2.61 (s, 6H), 3.83 (s, 3H), 6.6 (s, 2H), 10.5 (s, 1H).

Workup

stirringThe reaction mixture was stirred for 1 hour at -78° C. and for 1.5 hours at room temperature
washwashed with 300 mL of water
dry with materialThe organic portion was dried (MgSO4)
filtrationfiltered
customevaporated
customto give the crude product, which
customwas purified by flash column chromatography (silica gel, 90:10 hexane/ethylacetate)

Sources & evidence

ORD record: ord-947bd60bf08e41d287c640c0f7b79b6c
Source dataset: uspto-grants-2000_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06107517

Reaction notes

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