Sulfuric Acid → 6,8-Difluoro-3,4-dihydronaphthalen-1(2H)-one
Reaction equation
S(=O)(=O)(O)O.[F:6][C:7]1[CH:8]=[C:9]([CH2:14][CH2:15][CH2:16][C:17]([OH:19])=O)[CH:10]=[C:11]([F:13])[CH:12]=1>O>[F:13][C:11]1[CH:10]=[C:9]2[C:8](=[C:7]([F:6])[CH:12]=1)[C:17](=[O:19])[CH2:16][CH2:15][CH2:14]2Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 45 °C
Procedure
A mixture of concentrate sulfuric acid (10.21 kg) and crude 4-(3,5-difluoro-phenyl)-butyric acid (2.8 kg) was stirred at 45° C. until the cyclization reaction was complete by HPLC. The reaction mixture was diluted with water (6.15 kg), and the product was extracted with THF/methylene chloride (2.71/7.33 kg) mixture. The organic layer was sequentially washed with water (4 liters), saturated aqueous sodium bicarbonate (2.64 kg), water (3.0 kg) and 50% diluted brine (8.4 kg). Removal of the solvents provided 1.64 kg (62% yield) of 6,8-difluoro-3,4-dihydro-2H-naphthalen-1-one as a light yellow solid (92.75% pure by HPLC): MP=58.1-58.8° C.; MS (M+1)=183; H1 NMR (300 MHz): δ (DMSO): 2.00 (2H, p, J=6.4 Hz), 2.57 (2H, t, J=6.40 Hz), 2.96 (2H, t, J=6.40 Hz), 7.08-7.20 (2H, m, J=2.26 Hz).
Workup
- extractionthe product was extracted with THF/methylene chloride (2.71/7.33 kg) mixture
- washThe organic layer was sequentially washed with water (4 liters), saturated aqueous sodium bicarbonate (2.64 kg), water (3.0 kg) and 50% diluted brine (8.4 kg)
- customRemoval of the solvents
Sources & evidence
- ORD record
- ord-5cc35d7b0927463b9f5e1b78483e07f1
- Source dataset
- uspto-grants-2012_02
- Patent number
- US08119842B2
Reaction notes
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