4-BROMO-2-HYDROXYACETOPHENONE

White to yellow solid

Intermediate 9B:; [00217] Aluminum chloride (36 g, 270 mmol) was added to Intermediate 9A(32.0 g, 149 mmol) in a round bottom flask fitted with a reflux condenser, nitrogen gas inlet, and sodium hydroxide solution to scrub the HCl(g) effluent. The reaction flask was place in a 120 Commercially available 3-bromophenol (1, 50 g, 0.289 mol) was added to a mixture of AcCompound 15-2 (0413) To a stirred suspensions of compound 15-1 (46 g, 0.0.21 mol) and anhydrous aluminum chloride power (57 g, 0.42 mol) was heated to 160° C. for 3 h. The mixture reaction was cooled to room temperature and ice (200 g) and water (800 mL) was poured and purified with hydrochloric acid at pH 7. the reaction was extracted with ethyl acetate (500 mL×Fries migration of the same was carried out by heating with anhydrous aluminum chloride in o-dichlorobenzene for 8 hours to obtain the product in 70percent yield, which was condensed with N-bocpiperidone in methanol in the presence of pyrrolidine, and desired product Vb was obtained in 65percent yield.2. 2-hydroxy-4-bromoacetophenone was synthesized through the schematic pathway shown below. 3-Bromophenol was acylated with acetic anhydride in the presence of catalytic quantity of sulfuric acid to get the acylated product in quantitative yield. Fries migration of the same was carried out by heating with anhydrous aluminium chloride in o-dichlorobenzene for 8 h to get the product in 70 percent yield, which is condensed with N- bocpiperidone in methanol in the presence of pyrrolidine and desired product Vb was obtained in 65 percent yield.In a 250 mL round bottom flask (8) (5.49 g, 26 mmol) and anhydrous AlCl3-Bromophenol (5) (10.0 g, 58 mmol) was dissolved in pyridine(30 mL) under ice-bath and was stirred for 30 min. Acetic anhydride (8.3 mL, 88 mmol) was added dropwise into above mixture at the same temperature. The ice-bath was removed after dropping and the mixture was stirred for 2 h. Concentrated HCl and ice-water (300 mL) was added to neutralize pH to 7. The mixture was extracted with AcOEt (100 mL 3). The organic layer was collected and washed with brine and dried over NaTo a stirred solution of 4-Bromo-2-hydroxy-benzonitrile (3. 6 g, 18. 2MMOL) in anhydrous THF solution (20 mL) was added methylmagnesium bromide (1. 4 M in THF/toluene, 39.0 mL, 54. 6MMOL, 3 eq) at 0 °C under argon. The reaction mixture was slowly warm up to rt and stirred for 15 h. The mixture was cooled to 0 °C and quenched by the addition of water (5 mL) followed by concentrated HCI (10 mL). The resulting solution was refluxed for 2 h before cooled down to rt. The reaction mixture was then poured into EtOAc (100 mL) and water (100 mL). The layer was separated and the organic layer was washed with water (2 x 50 mL), dried over NA2SO4, filtrated, and concentrated under reduced pressure. The residue was then subjected to silica gel chromatography (20percent EtOAc/Hexane) to provide 1- (4-BROMO-2-HYDROXY-PHENYL)- ethanone (2.81 g, 71.9percent) as yellow OIL. 1H-NMR (CDCI3) : 8 12.32 (s, 1H, OH), 7.57 (d, J = 8. 7HZ, 1H), 7.17 (d, J = 1, 9 Hz, 1H), 7.03 (dd, J = 1.9, 8.7 Hz, 1H), 2.62 (s, 3H).Intermediate 2: (E)-3-{4-Oxo-spiro[chromane-2, 4'-piperidine]-7-yl}-acrylic acid methyl ester [Show Image] STEP A 3-Bromo-phenol (10.0 g, 57.8 mmol) was dissolved in 10 ml of pyridine and 10 ml of acetic anhydride and stirred overnight at RT. The mixture was than poured into water, and 1 M HCl was added until reaching a neutral pH value. Extraction with AcOEt furnished a crude product, which was treated with AlClA dichloroethane solution (250 ml) of 1-bromo-3-methoxybenzene (30 g), acetyl chloride (15.5 g) and aluminum chloride (25.6 g) was refluxed for 4 hours. The reaction mixture was poured into ice water, and the organic layer was separated. The organic layer was washed with water, dried over magnesium sulfate and then concentrated. The residue was subjected to silica gel chromatography, and the title compound was obtained as a colorless oil (14.4 g, yield 42percent) from the diethyl ether-hexane (1:10) eluate. Reference Example 101

Molecular Weight:215.04
XLogP3:2.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:213.96294
Monoisotopic Mass:213.96294
Topological Polar Surface Area:37.3
Heavy Atom Count:11
Complexity:158
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes