2-CHLORO-4,5-DIFLUOROANILINE

General procedure: Different substituted anilines 3 (10.0mmol) were added to a solution of hydrochloric acid (15mL, 3-4mol L-1), and then sodium nitrite (0.76g, 10.5mmol) dissolving in water (3mL) was dropwise added at 0C. After 0.5h, tin (II) chloride (4.5g, 20mmol) in 10mL of concentrated hydrochloric acid was dropwise added to the above mixture. The reaction was vigorously stirred for 2h at 0C, and then was filtered and washed with 3-4molL-1 hydrochloric acid. The precipitate was dissolved in water and filtered. The filtrate was adjusted to pH 12, and the generated solid was collected and dried to afford different substituted phenylhydrazine 4a-k.[ithium 1, 1, 1 , 3, 3, 3-hexamethyldisilazan-2-ide (42 ml, 1 M solution in tetrahydrofuran, 42 mmol, CAS No 4039-32-1) was added drop wise within 5 minutes to a solution of 2-chloro- 4, 5-difluoroaniline (3.88 g, 23.2 mmol) in tetrahydrofuran (110 ml) at -780 and the mixture was stirred for 1 h at that temperature. A solution of ethyl 4-{[tert-butyl(diphenyl)silyl]oxy}-1 - (2-chloroethyl)cyclohexanecarboxylate (10.0 g, 21.1 mmol) in tetrahydrofuran (110 ml) wasadded and the mixture was stirred for 2 h at -78G. The mixture was warmed to room temperature and stirred for 4 d. For work-up, the reaction mixture was added to a mixture of water and sodium bicarbonate solution and the mixture was extracted with ethyl acetate (3x). The combined organic phases were washed with sodium chloride, dried over sodium sulfate and concentrated under reduced pressure, the residue was purified by flash chromatography (340 g Snap cartridge, hexane/ethyl acetate gradient, 5% -> 25% ethyl acetate). The productcontaining fractions were concentrated and were purified a second time by flash chromatography (120 g Snap cartridge, hexane/ethyl acetate gradient, 5% -> 25% ethyl acetate) to give the title compound in 2 fractions: fraction 1 (7.53 g, single isomer based on 1H NMR, isomer 1, contains impurities from aniline and isomer 2), fraction 2(1.13 g, isomer2).Fraction 1 (isomer 1): 1H-NMR (400 MHz, DMSO-d6): 6 [ppm] = 7.67-7.55 (m, 5H), 7.52-7.30 (m, 9H), 3.97 (brs, 1H), 3.60 (t, 2H), 2.15-2.07 (m, 2H), 2.04 (t, 2H), 1.76-1.63 (m, 2H), 1.58- 1.45 (m, 2H), 1.39-1.27 (m, 2H), 1.05 (5, 9H).[C-MS (Method 1): R = 1.80 mm; MS (ESIpos): m/z = 518.3 [M÷H]Lithium 1, 1, 1, 3, 3, 3-hexamethyldisilazan-2-ide (42 ml, 1 M solution in tetrahydrofuran, 42 mmol, CAS No 4039-32-1 ) was added drop wise within 5 minutes to a solution of Lithium bis(trimethylsilyl)amide (46 ml, 1.0 M, 46 mmol) was added during 5 minutes drop wise to a solution of

Molecular Weight:163.55
XLogP3:2.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:163.0000331
Monoisotopic Mass:163.0000331
Topological Polar Surface Area:26
Heavy Atom Count:10
Complexity:122
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes