Phosphorus oxide (P4O10) → 6,8-Difluoro-3,4-dihydronaphthalen-1(2H)-one

Temperature

65 °C

This step follows the general procedure reported by Eaton et al., Organic Chemistry 38 (23): 4071-4073 (1973). Eaton's reagent, prepared from 32 g phosphorus pentoxide and 192 mL methanesulfonic acid, was heated at 65° C. A solution of 4-(3,5-difluoro-phenyl)-butyric acid (12.85 grams, 64.19 mmoles, prepared as described by Repke et al., U.S. Pat. No. 5,538,988) in 30 mL methanesulfonic acid was added and the reaction mixture was heated at 65° C. for 35 minutes. The mixture was poured onto 1 L cracked ice and the product was extracted twice with 500 mL of a mixture of 2 parts diethyl ether to 1 part ethyl acetate. The organic phase was washed with saturated sodium bicarbonate, water, saturated sodium chloride and then it was dried (magnesium sulfate). The solution was concentrated under reduced pressure. 6,8-Difluoro-3,4-dihydro-2H-naphthalen-1-one was isolated by recrystallization from hexane, 9.55 grams (82%), m.p. 57-58° C.

1. temperaturethe reaction mixture was heated at 65° C. for 35 minutes
2. additionThe mixture was poured onto 1 L
3. extractionthe product was extracted twice with 500 mL of a mixture of 2 parts diethyl ether to 1 part ethyl acetate
4. washThe organic phase was washed with saturated sodium bicarbonate, water, saturated sodium chloride
5. dry with materialit was dried (magnesium sulfate)
6. concentrationThe solution was concentrated under reduced pressure

ORD record

ord-6ca06523b87348188e795fe659fbe018

Source dataset

uspto-grants-2011_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07981923B2