Acetic Acid → 2,3-Difluoro-6-methoxybenzaldehyde

Temperature

-75 °C

A solution of lithium diisopropylamide, 2M in TBF/n-heptane (171 mL, 341 mmol) was further diluted with dry THF (250 mL) and cooled under nitrogen to −75° C. 3,4-Difluoroanisole (46.8 g, 325 mmol) in dry THF (100 mL) was added dropwise and the mixture stirred at −75° C. for 1 h. Dry N,N-dimethylformnamide (27.6 mL, 358 mmol) was added dropwise and the mixture stirred for 10 mins at −70° C. Acetic acid (30 mL) and water (400 mL) were added, warming the temperature to 10° C. Extracted into diethyl ether (2×300 mL). Combined extracts were washed with water (250 mL), aqueous hydrochloric acid (0.2 N, 400 mL) and brine (2×250 mL), dried (MgSO4) and the solvent evaporated in vacuo to give a red/orange oil which crystallised. Purification was by recrystallisation from diethyl ether/petroleum ether 40-60 to give (53.0g, 95%) of solid; δH (300 MHz, CDCl3) 10.40 (1H, s, CHO), 7.37 (1H, q, ArH), 6.71 (1H, m, ArH), and 3.93 (3H, s OCH3).

1. additionDry N,N-dimethylformnamide (27.6 mL, 358 mmol) was added dropwise
2. stirringthe mixture stirred for 10 mins at −70° C
3. temperaturewarming the temperature to 10° C
4. extractionExtracted into diethyl ether (2×300 mL)
5. washCombined extracts were washed with water (250 mL), aqueous hydrochloric acid (0.2 N, 400 mL) and brine (2×250 mL)
6. dry with materialdried (MgSO4)
7. customthe solvent evaporated in vacuo
8. customto give a red/orange oil which
9. customcrystallised
10. customPurification
11. customwas by recrystallisation from diethyl ether/petroleum ether 40-60

ORD record

ord-94d7fc2ec38242f6b87c342c8afc74d9

Source dataset

uspto-grants-2008_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07417064B2