5-BROMO-2-CHLOROBENZYL ALCOHOL97

To a solution of 5-bromo-2-chlorobenzoic acid (5 g, 21 .23 mmol), in tetrahydrofuran (THF)(10 mL), 10 M borane-methyl sulfide complex (2.123 mL, 21.23 mmol) was added at 0°C.The reaction was then warmed to 23°C and stirred for 14h. The reaction mixture was cooled and additional 10 M borane-methyl sulfide complex (1 .062 mL, 10.62 mmol) was added to the reaction mixture. Afterwards, the reaction was cooled on an ice water bath and methanol (2.00 mL) was added slowly. When most of the bubbling ceased the volatile solvents wereremoved in vacuo and the residue was dissolved in EtOAc (1 OmI) and washed with saturated aq. NaHCO3. The aqueous layer was back extracted with EtOAc (50m1) and the combined EtOAc layers were washed with water (5m1) and saturated aq. NaCI, dried with Na2SO4 and concentrated to afford the title compound. (4.62 g, 98percent yield) 1H NMR (400 MHz, METHANOL-d4) 3 7.70 (5, 1H), 7.40 (d, J=8.28 Hz, 1H), 7.28 (d, J=8.53 Hz, 1H), 4.66(5, 2H)Intermediate 1: Preparation of (ZR^R^R^-y^-^-Z-Cacetoxymethyli-i-iS- (bromomethyl)-4-chlorophenyl)tetrahydro-2H-pyran-3, 4, 5-triyl triacetateStep 1: Preparation of (5-bromo-2-chlorophenyl) methanol 5-bromo-2-chlorobenzoic acid (20 g, 84.92 mmol) in dry THF (50 mL) was added to a solution of sodium borohydride (8 g, 212.34 mmol) in dry THF (128 mL) in 15 min at r.t. To the resulting reaction mixture a solution of Iodine (26.85 g, 106.15 mmol) in dry THF (170 mL) was added in another 15 min. Stirring was continued till the Iodine color disappeared after which the reaction mixture was heated to reflux temperature for 18 h. After completion of the reaction as confirmed by TLC, volatiles were evaporated in vacuo. The residue obtained was dissolved in ethyl acetate (200 mL), washed with a saturated solution of NaHS0Step 1: Preparation of (5-bromo-2-chlorophenyl) methanol 5-bromo-2-chlorobenzoic acid (20 g, 84.92 mmol) in dry THF (50 mL) was added to a solution of sodium borohydride (8 g, 212.34 mmol) in dry THF (128 mL) in 15 min at r.t. To the resulting reaction mixture a solution of Iodine (26.85 g, 106.15 mmol) in dry THF (170 mL) was added in another 15 min. Stirring was continued till the Iodine color disappeared after which the reaction mixture was heated to reflux temperature for 18 h. After completion of the reaction as confirmed by TLC, volatiles were evaporated in vacuo. The residue obtained was dissolved in ethyl acetate (200 mL), washed with a saturated solution of NaHS0Step 1: 2-Chloro-5-bromobenzoic acid (4.0 g, 0.0170 mol) was dissolved in anhydrous tetrahydrofuran (24 ml) Argon gas was added dropwise dimethyl sulfide borane (8.7ml, 0.0849mmol) at 0°C, After 5 hours at room temperature, TLC (thin layer chromatography) to complete the reaction, ice-water bath, slowly dropping water, Extracted with ethyl acetate and dried to give 3.6 g of a white solid, which was taken directly to the next step.Take 5-bromo-2-chlorobenzaldehyde 108 kg, dissolved in 250 kg of anhydrous ethanol, add 25 kg of sodium borohydride, react at room temperature for 4 hours, after the end of the reaction, vacuum recovery of most of the anhydrous ethanol, The reaction system was quenched with dilute hydrochloric acid dropwise on an ice bath, and the system was extracted with ethyl acetate at a pH of 4-5 and 300 kg, washed with water until neutral, dried over anhydrous sodium sulfate, filtered, and the filtrate was recovered under reduced pressure.Petroleum ether: Ethyl acetate (1:1) was recrystallized to obtain a pale yellow solid powder (107 kg) with a yield of 99percent.Take 108 kg of 5-bromo-2-chlorobenzaldehyde, dissolve in 250 kg of absolute ethanol, add 25 kg of sodium borohydride, and react at room temperature for 4 h.After the reaction is completed, most of the anhydrous ethanol is recovered under reduced pressure, and the reaction system is quenched by dropwise addition of dilute hydrochloric acid in an ice bath, and the pH of the system is 4-5.Extracted with 300 kg of ethyl acetate, washed with water until neutral, dried over anhydrous sodium sulfate, filtered, and the filtrate was evaporated under reduced pressure, petroleum ether: acetic acidThe ethyl ester (1:1) was recrystallized to obtain 107 kg of a pale yellow solid powder, yield 99percent.Example 1B Preparation 13. (5-bromo-2-chlorophenyl)methanolTo a THF (50 mL) solution of methyl 5-bromo-2-chlorobenzoate (Preparation 12, 10.5 g, 42 mmol) was added sodium borohydride (3.18 g, 84 mmol) followed by the careful dropwise addition of MeOH (7 mL) over 30 minutes. The reaction was stirred for one hour at room temperature. An additional amount of sodium borohydride (0.5 g) was added and the mixture stirred for one more hour at room temperature. The reaction mixture was poured into ethyl acetate (125 mL) and stirred for twenty minutes. Water (50 mL) was added, slowly at first, then all at once. The layers were stirred vigorously together for fifteen minutes. The organic phase was collected, dried over sodium sulfate, and concentrated at low pressure to give (5-bromo-2-chlorophenyl)methanol as a white solid (7.85 g, 84percent).

Molecular Weight:221.48
XLogP3:2.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:219.92906
Monoisotopic Mass:219.92906
Topological Polar Surface Area:20.2
Heavy Atom Count:10
Complexity:110
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes