Dimethylformamide → 2,3-Difluoro-6-methoxybenzaldehyde

Temperature

-75 °C

A solution of lithium diisopropylamide, 2M in THF/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-dimethylformamide (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 (53.0 g, 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. stirringthe mixture stirred for 10 mins at −70° C
2. temperaturewarming the temperature to 10° C
3. extractionExtracted into diethyl ether (2×300 mL)
4. washCombined extracts were washed with water (250 mL), aqueous hydrochloric acid (0.2 N, 400 mL) and brine (2×250 mL)
5. dry with materialdried (MgSO4)
6. customthe solvent evaporated in vacuo
7. customto give a red/orange oil which
8. customcrystallised
9. customPurification
10. customwas by recrystallisation from diethyl ether/petroleum ether 40–60

ORD record

ord-18aa208b5e6843b98e142838e9d040e7

Source dataset

uspto-grants-2006_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07037932B2