2-Fluoro-4-hydroxybenzaldehyde

To a 2000 mL dry round bottom flask were added 2-fluoro-4-methoxybenzaldehyde (25.0 g, 162.2 mmol), anhydrous AlClTo a -70 To a -70 Intermediate 24. 5-bromo-2-fluoro-4-hydroxybenzaldehyde (24); [0196] To the solution of 2-fluoro-4-methoxybenzaldehyde (3 g, 19.5 mmol, 1 eq., Aldrich, Milwaukee, WI, USA) in DCM (80 mL) was added dropwise BBr[0155] To the solution of 2-fluoro-4-methoxybenzaldehyde (3 g, 19.5 mmol, 1 eq.) in DCM (80 mL) was added dropwise BBrGeneral procedure: Acetamide (1.18 g, 0.02 mol) was dissolved in glacial acetic acid (4.20 g, 0.07 mol), and the solution was cooled down using ice bath. At 0 C, acetyl chloride (0.78 g, 0.01 mol) was added, and formation of crystalline product was obtained. Mixture was stirred by 15-20 min, and appropriate aldehyde(0.01 mol) was added dropwise. After 30 min of additional stirring in ice bath, it was removed, and the reaction mixture was stirred at room temperature for 24 h. Then the content of flask was cooled again to 0 C, and phosphorus trichloride(1.37 g, 0.01 mol) was added dropwise. After 30 min of stirring in 0 C, the mixture was left to reach room temperature and then was heated for 1-2 h at 75-80 C. Evaporation of the volatile components of the reaction mixture resulted in an oily product, which was refluxed for 6-8 h in concentrated HCl (30 mL). Volatile components of the reaction had been evaporated, and the resulting oily or solidified residue was dissolved in 20 ml of ethanol. The insoluble precipitate (ammonium chloride) was filtered off, and evaporation of solvent gave white precipitate, which was recrystallized from ethanol and water. Crystals suitable for X-ray single crystal diffraction were obtained by cooling solutions of compounds in water/ethanol mixture from 60 C to room temperature and then left at 4 C.A mixture of 3-fluoro-4-hydroxybenzaldehyde (1.4 g, 10 mmol) and morpholine (1.3 g, 15 mmol) in DCM (30 mL) was stirred for 0.5 h then NaBH3CN (1.3 g, 20 mmol) was added. After 0.5 h, the mixture was washed with water and the organic layer was concentrated. The residue was purified using silica gel eluting with PE/EA (1:1) to give 3-fluoro- 4-(morpholinomethyl)phenol (1.1 g, 52% yield) as an oil. MS (ESI) m/z 212 [M+H] +.

Molecular Weight:140.11
XLogP3:1.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:140.02735756
Monoisotopic Mass:140.02735756
Topological Polar Surface Area:37.3
Heavy Atom Count:10
Complexity:127
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes