2-(2-Bromophenyl)-2-propanol

General procedure: A 38percent solution of ammonium chloride, 58 mL, was added at –5 °Cto the product obtained by reaction of 26.50 g (0.14 mol) of ester 4a in 35 mL of anhydrous diethylether with methylmagnesium iodide [prepared from 9.1 g (0.37 mol) of magnesium and 53.3 g (0.37 mol) of freshly distilled methyl iodide in 85 mL of anhydrous diethyl ether]. The ether layer was separated by decanting, and the pasty precipitate was extracted with diethyl ether (3 × 35 mL). The extracts were combined, dried over Na2SO4, and evaporated. Yield 19.40 g (82percent), purity 95percent (GLC), bp 99–100°C (5 mm), d420 =1.1576, nD20 = 1.5420; MRD 46.43, calcd. 46.55;published data [19]: mp 23.7°C, bp 79.2°C (2.2 mm), nD20 = 1.5416. IR spectrum, ν, cm–1: 3460, 1175 (OH), 1370, 1385 [C(CH3)2], 690 (C–Cl). 1H NMR spectrum, δ, ppm: 1.64 s (6H, CH3), 2.46 s (1H, OH), 6.9–7.7 m(4H, Harom). Found, percent: C 63.00; H 6.42; Cl 20.71.C9H11ClO. Calculated, percent: C 63.35; H 6.50; Cl 20.78.A 12-Liter 4-neck flask equipped with a thermocouple, condenser, septum, addition funnel and overhead mechanical stirrer under argon was charged with methyl-2-bromobenzoate (226.5 g, 1.05 mol) and THF (1.6 L, 19.66 mol). The mixture was cooled to a temperature between 2 and 5° C. with stirring and held for 30 min. To the solution was slowly added methyl magnesium bromide in diethyl ether (3M, 1.05 L; 3.15 mol) via the addition funnel at a rate to maintain the reaction temperature below 15° C. An exotherm was observed during the addition, the reaction temperature warmed from 3 to 15° C. The addition of 1.05 L Grignard was complete in 4 h (approximate feed rate was 4.17 mL/min). The reaction mixture appeared to be off-white/yellow slurry. The reaction was allowed to warm to room temperature and stirred overnight (15 h). The reaction was sampled by HPLC/TLC and showed no starting material present. The ice bath was again applied to the reaction flask and a 0.5 M HCI solution (4.5 L; 2.25 mol) was slowly added over a period of 2 h. The temperature increased dramatically from 0 to 15° C. After the quench was complete, the reaction was stirred at room temperature for 30 min. Additional 2 N HCl (500 mL; 1.00 mol) was slowly added to maintain a pH less than 6. MTBE (1 L) was added to help with the phase split. The reaction was stirred at room temperature for 1 to 2 h to dissolve the solid material into the aqueous phase (most likely Mg(OH)Scheme 17 XCVIII XCVIIStep 1[00252] To a stirring solution of methyl 2-bromobenzoate (XCIV) (5 g, 0.0233 mol) in THF (30 mL) under argon at 0°C was added dropwise MeMgBr (19.4 mL, 0.058 mol), maintaining the temperature in the range of -5 to 0°C. The reaction mixture was stirred at 0°C for 1 hour and then at room temperature overnight. The mixture was cooled to 0°C and 1M aqueous HCl (35 mL) was added, maintaining the temperature below 5°C, after which it was allowed to reach room temperature and was stirred for 30 minutes. To this mixture EtOAc (35 mL) was added and after stirring for 5 minutes a white precipitate was removed by filtration through a Celite pad. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic fractions were concentrated, washed with brine and dried over MgSC^. Crude XCV was purified by silica gel chromatography using DCM then DCM/MeOH 300/1 to give 2- (2-bromophenyl)propan-2-ol (XCV) as a light yellow oil (4.55 g; 21.2 mmol, 91percent yield). 1H NMR (CDCls) δ ppm 1.75 (s, 6H), 2.85 (brs, 1H), 7.09 (td, J=7Hz, J=2Hz, 1H), 7.29 (td, J=7Hz, J=lHz, 1H), 7.58 (dd, J=7, J=l, 1H), 7.67 (dd J=7, J=2, 1H).To a solution of methyl 2-bromobenzoate (20.76 g, 96 mmol) in 120 mL of anhydrous ether under Argon at 0° C. was slowly added methylmagnesium bromide (77 mL, 3.26 M) at a rate that the internal temperature of the mixture was below 20° C. A white suspension resulted, and the mixture was stirred at room temperature for 2 h. The mixture was cooled in an ice-water bath. To the reaction mixture was very slowly added hydrochloric acid (400 mL, 0.5 M). The pH of the final mixture was adjusted to less than about 6 with few drops of 2M hydrochloric acid. The layers were separated, and the aqueous layer was extracted twice with ether. The organic layers were combined and dried over magnesium sulfate. The organic fraction was filtered, and the filtrate was concentrated to yield the title compound as a pale yellow liquid, which was distilled under vacuum to afford the title Compound 10d as a colorless liquid (16.9 g, 82percent, b.p. about 65-70° C./0.3 mmHg). Methylmagnesium bromide in toluene/THF (1.4 M, 1.24 L) was charged to a vessel under a nitrogen atmosphere. Methyl 2-bromobenzoate (164 g) was added. The reaction mixture was aged at 35-40 °C and assayed for completion. Ethanol (57.3 mL) was added. The mixture was aged at 45 °C for 1h. A solution of pyridine-4-carboxaldehyde (8.09 g) in toluene (16 mL) was added. The mixture was aged at 45-50 °C. A vessel was charged with water (820 mL) and 37percent hydrochloric acid (186 mL) and cooled to 0 °C. The reaction solution was added into the cold aqueous hydrochloric acid solution. The mixture was aged at 20-25 °C, and the lower aqueous layer cut. The organic layer washed with water and the lower aqueous layer cut. The organic layer was concentrated under reduced pressure at 40-50 °C. DMF (-200 mL) was added and concentration continued to afford -303 g solution of IIA as a slightly cloudy oil. To a stirred solution of ethyl 2-bromobenzoate (10 g, 46.5 mmol) in tetrahydrofuran (80 mL) was added dropwise a 3.0 M solution of methylmagnesium chloride in tetrahydrofuran (39 mL, 0.116 mol) at room temperature and the mixture was stirred for 19 h at the same temperature. The reaction mixture was quenched by the addition of 2 N hydrochloric acid aqueous solution, and concentrated to give a colorless residue. The crude material was partitioned between diethyl ether and water, and then the organic layer was washed with brine, dried over sodium sulfate, and evaporated. The residue was purified by column chromatography on silica gel (150 g) eluting with hexane/ethyl acetate (15/1) to afford 6.91 g (69percent) of the title compound as a colorless oil: 'H-NMR (CDCl3) 8 7.68-7. 57 (2H, m), 7. 33-7. 25 (1H, m), 7.13-7. 07 (1H, m), 1.75 (6H, s).[0383] A 500 mL round-bottomed-flask equipped with a magnetic stir bar and ice- H

Molecular Weight:215.09
XLogP3:2.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:213.99933
Monoisotopic Mass:213.99933
Topological Polar Surface Area:20.2
Heavy Atom Count:11
Complexity:134
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes