4-Bromo-3-methoxybenzaldehyde

3C. 4-Bromo-3-methoxy-benzaldehydeA mixture of 4-amino-3-methoxy-benzaldehyde (4.5 g, 29.8 mmol), n-butyl nitrite (4.6 g, 35.8 mmol) and copper bromide (6.83 g, 47.7 mmol) in MeCN (45 mL) was stirred atroom temperature for 12 hours. The reaction mixture was diluted with EtOAc (100 mL), washed with water (200 mL), dried (Na2SO4) and evaporated under reduced pressure to leave a residue which was purified by column chromatography on neutral silica gel (60-120 mesh) using 0-70percent EtOAc/hexanes as the eluentto give the title compound (4.2 g, 66percent).(c) . 4-Bromo-3-methoxy-benzaldehyde A solution of the product of example 42b (38.3 g) in acetonitrile (600 ml) was added dropwise to a mixture of n-butyl nitrite (43.1 ml) and copper(l) bromide (63.6 g) in acetonitrile (1300 ml). After stirring for 18 h at room temperature, the reaction mixture was diluted with ethyl acetate and washed with an aqueous 1 M HCI solution. The organic layer was separated and washed with brine, dried (MgS0To a solution of 4-bromo-3-methoxy benzonitrile (0.38 g, 1.8 mmol) obtained above in toluene (25 mL) was added DIBAL-H (1.0 M in THF) ML, 3.6 mmol) at -78°C. After stirring at the same reaction temperature for 30 minutes, the reaction temperature is raised to room temperature and stirring is continued for 5 hours. To terminate the reaction, methanol (15 ML) is added and further stirred for 30 minutes. Add 10percent sulfuric acid (10 mL) and extract with ethyl acetate. Magnesium sulfate is added to the extracted organic layer to remove water and concentrated under reduced pressure. The concentrate was concentrated under reduced pressure and purified by silica gel column chromatography (hexane: ether = 4: 1) to obtain 4-bromo-3-methoxybenzaldehyde in the form of a white powder 41percent yield)General procedure: To a stirred solution of starting compound (0.5–1.2 mmol) in DMF–H (400 mg, 1.0 equiv) and TMSCF3 (1.5 equiv) was dissolved in dry THF (15 mL), cooled with ice-water under N2. To the mixture was added CsF (1.0 equiv). The mixture was stirred at rt for 2h. The reaction was quenched with 1M HC1 (30 mL). The mixture was extracted with ethyl acetate and hexane (1 :4). The crude mixture was purified on a silica gel column to provide l-(4-bromo-3-methoxyphenyl)-2, 2, 2-trifluoroethan-l-ol (280 mg).A mixture of synapaldehyde (210mg, 1.0mmol), 4-bromo-3-metoxybenzaldehyde (450mg, 2.0mmol), copper powder (230mg, 4.0mg atom, 99.5percent purity), and N, N-dimethyl acetamide (2mL) was heated to 160°C in a sealed tube under a nitrogen atmosphere for 21h. The mixture was then allowed to cool (20°C) and diluted with ethyl acetate prior to filtration. The filtrate was partitioned between ethyl acetate and water in a separatory funnel, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine and dried over anhydrous Na2SO4. Evaporation of the extract and purification of the residue by column chromatography (benzene:ethyl acetate=4:1) on silica gel gave dialdehyde 4 as a pale yellow powder (75mg, 0.22mmol, 22percent). Mp 185°C. IR (Diamond ATR): 1673, 1587, 1484, 1398, 1247, 1218, 1120, 1032 cm'1. 1H NMR (400MHz, CDCl3): delta 3.82 (3H, s), 3.83 (6H, s), 6.61 (1H, d, J=8.9Hz), 6.70 (1H, dd, J=15.2, 7.7Hz), 6.86 (2H, s), 6.98 (1H, dd, J=8.9, 3.4Hz), 7.37 (1H, d, J=3.4Hz), 7.45 (1H, d, J=15.2Hz), 9.73 (1H, d, J=7.7Hz), 10.70 (1H, s). 13C NMR (100MHz, CDCl3): delta 55.8, 56.3, 105.5, 107.0, 109.4, 116.7, 123.3, 125.4, 128.8, 131.7, 135.2, 152.0, 153.7, 154.8, 189.6, 193.3. HRMS m/z 365.0975 [(M+Na)+; calcd for C19H18O6Na+: 365.0996].

Molecular Weight:215.04
XLogP3:2.3
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:213.96294
Monoisotopic Mass:213.96294
Topological Polar Surface Area:26.3
Heavy Atom Count:11
Complexity:138
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes