(2-bromo-5-fluorophenyl)methanol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (2-bromo-5-fluorophenyl)methanol (11, 4.10 g, 20.0 mmol) in dry DME (40 mL) at 0° C. was added a solution of PBr3 (3.25 g, 12.0 mmol) in dry DME (40 mL) dropwise. The mixture was then slowly warmed up to RT and stirred at for another 3 h. The mixture was diluted with water (100 mL), and extracted with 1:1 petroleum-ether-EtOAc (100 mL×2). The combined extracts were washed with saturated NaHCO3 and brine, dried over MgSO4 and concentrated to give 1-bromo-2-(bromomethyl)-4-fluorobenzene (12). extracted with 1:1 petroleum-ether-EtOAc (100 mL×2) The combined extracts were washed with saturated NaHCO3 and brine dried over MgSO4 concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 2-bromo-5-fluorobenzoate (10, 21.30 g, 91.4 mmol) in dry THF (150 mL) was added NaBH4 (6.95 g, 183 mmol). Methanol (20 mL) was added dropwise at RT. After the addition, the mixture was stirred at RT for 1 h. Water (200 mL) was slowly added. The mixture was extracted with CH2Cl2 (100 mL×2). The combined extracts were washed with saturated NaHCO3 and brine, dried over MgSO4 and concentrated to give (2-bromo-5-fluorophenyl)methanol (11). After the addition The mixture was extracted with CH2Cl2 (100 mL×2) The combined extracts were washed with saturated NaHCO3 and brine dried over MgSO4 concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-bromo-5-fluoro-benzaldehyde (21.34 g, 105 mmole) in methanol (170 mL) was added at 0-5° C. portionwise NaBH4 (3.99 g, 105 mmole). At the end of the addition, the cooling bath was removed and the reaction mixture was stirred at room temperature for 2 h. On concentration, the solution generated a white solid that was added with water, filtered and dried under vacuum to yield compound PRE7 (19.23 g; white powder) (Yield=91 Rt: 10.64 min. At the end of the addition the cooling bath was removed On concentration that was added with water filtered dried under vacuum to yield compound PRE7 (19.23 g; white powder) ( Yield=91 Rt: 10.64 min.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Dissolve commercially available (2-bromo-5-fluoro-phenyl)-methanol (4.8 g, 23.4 mmol) in methylene chloride (100 mL) and cool to 0° C. Add PPTS (590 mg, 2.3 mmol) followed by ethyl vinyl ether (3.4 mL, 35.1 mmol). Warm reaction to room temperature slowly after addition. After 4 hours, pour the reaction into saturated aqueous sodium bicarbonate and extract with methylene chloride. Dry with sodium sulfate, filter and concentrate in vacuo to yield 5.4 g (83%) of the title compound as a clear and colorless oil. 1H NMR (CDCl3) 37.47 (dd, J=8.6, 5.0 Hz, 1M), 7.27 (dd, J=9.6, 3.1 Hz, 1H), 6.87 (td, J=8.0, 3.1 Hz, 1H), 4.89 (q, J=5.5 Hz, 1H), 4.65 (d, J=13.8 Hz, 1H), 4.54 (d, J=13.8 Hz, 1H), 3.70 (m, 1H), 3.55 (m, 1H), 1.42 (d, J=5.5 Hz, 3H), 1.22 (t, J=7.2 Hz, 3H). Warm reaction to room temperature slowly after addition pour extract with methylene chloride Dry with sodium sulfate filter concentrate in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (2-bromo-5-fluorophenyl)methanol (11, 4.10 g, 20.0 mmol) in dry DME (40 mL) at 0° C. was added a solution of PBr3 (3.25 g, 12.0 mmol) in dry DME (40 mL) dropwise. The mixture was then slowly warmed up to RT and stirred at for another 3 h. The mixture was diluted with water (100 mL), and extracted with 1:1 petroleum-ether-EtOAc (100 mL×2). The combined extracts were washed with saturated NaHCO3 and brine, dried over MgSO4 and concentrated to give 1-bromo-2-(bromomethyl)-4-fluorobenzene (12). extracted with 1:1 petroleum-ether-EtOAc (100 mL×2) The combined extracts were washed with saturated NaHCO3 and brine dried over MgSO4 concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (2-bromo-5-fluorophenyl)methanol (11, 4.10 g, 20.0 mmol) in dry DME (40 mL) at 0° C. was added a solution of PBr3 (3.25 g, 12.0 mmol) in dry DME (40 mL) dropwise. The mixture was then slowly warmed up to RT and stirred at for another 3 h. The mixture was diluted with water (100 mL), and extracted with 1:1 petroleum-ether-EtOAc (100 mL×2). The combined extracts were washed with saturated NaHCO3 and brine, dried over MgSO4 and concentrated to give 1-bromo-2-(bromomethyl)-4-fluorobenzene (12). extracted with 1:1 petroleum-ether-EtOAc (100 mL×2) The combined extracts were washed with saturated NaHCO3 and brine dried over MgSO4 concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 2-bromo-5-fluorobenzoate (10, 21.30 g, 91.4 mmol) in dry THF (150 mL) was added NaBH4 (6.95 g, 183 mmol). Methanol (20 mL) was added dropwise at RT. After the addition, the mixture was stirred at RT for 1 h. Water (200 mL) was slowly added. The mixture was extracted with CH2Cl2 (100 mL×2). The combined extracts were washed with saturated NaHCO3 and brine, dried over MgSO4 and concentrated to give (2-bromo-5-fluorophenyl)methanol (11). After the addition The mixture was extracted with CH2Cl2 (100 mL×2) The combined extracts were washed with saturated NaHCO3 and brine dried over MgSO4 concentrated