3-Bromo-2,6-difluorobenzoic acid

Off-white powder

6-fluoro-9-furan-3-yl-2, 3, 4, 5-tetrahydro-1, 4-benzoxazepine hydrochloride; (1) 3-bromo-2, 6-difluorobenzoic acid; To a mixed solution of 1.6N solution of n-butyllithium in hexane (9.4 ml, 15.0 mmol) and tetrahydrofuran (20 ml) were successively added 2, 2, 6, 6-tetramethylpiperidine (2.50 ml, 15.0 mmol) and 1-bromo-2, 4-difluorobenzene (2.90 g, 15.0 mmol) at -78°C, and the mixture was stirred at -78°C for 1 hr. The pulverized dry ice (5 g) was added, and the mixture was stirred at -78°C for 2 hr. Saturated aqueous ammonium chloride solution (5 ml) was added to the reaction mixture, and the mixture was stirred at room temperature for 30 min. Water (10 ml) and 1N hydrochloric acid (30 ml) were added, and the mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. Hexane was added to the residue, and desired product (2.30 g, 64.6percent) was collected by filtration as a solid. Step 1. To a round bottom flask containing Step 1. Preparation of bromo-2, 6-difluorobenzoic acid To an oven dried 2-necked round bottom flask under Argon at room temperature was added diisopropylamine (8.1 mL, 57.0 mmol) and THF (260 mL). The solution was cooled to -70 C. in a dry ice-acetone bath. n-Butyllithium (2.0 M in cyclohexane, 25.9 mL, 51.8 mmol) was added indropwise via syringe and the resulting reaction was warmed to 0 C. briefly then cooled back to -70 C. To this cold solution was added 1-bromo-2, 4-difluorobenzene (5.9 mL, 52.0 mmol) dropwise via syringe. After addition, the reaction was maintained at -70 C. for 1 hour. Carbon dioxide (5-9 g pieces, previously rinsed with dry THF) were added to the solution. The Ar balloon was removed and replaced with a bubbler to allow venting. The resulting reaction was then allowed to warm to room temperature and was quenched with a saturated aqueous NH4Cl solution to pH-7-8. The aqueous mixture was washed with EtOAc, acidified with aqueous 6 N HCl solution to pH-2-3, and extracted with EtOAc. The organic extract was washed with brine, dried (Na2SO4), filtered and concentrated in vacuo to afford 10.9 g (89%) of (2) N-benzyl-3-bromo-2, 6-difluoro-N-(2-hydroxyethyl)benzamide; To a solution of Example 67; 6-fluoro-9-furan-3-yl-2, 3, 4, 5-tetrahydro-1, 4-benzoxazepine hydrochloride; (1)

Molecular Weight:237.00
XLogP3:2.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:235.92845
Monoisotopic Mass:235.92845
Topological Polar Surface Area:37.3
Heavy Atom Count:12
Complexity:188
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes