3,4,5-Trimethoxybenzyl bromide

General procedure: benzyl alcohols (1 mmol) in dry benzene (15 mL) and phosphorus tribromides (0.5 mL) and stirred at room temperature to get respective benzyl bromides in quantitative yields, usual work-up.3, 4, 5-Trimethoxybenzyl alcohol (5.05 g, 25.5 mmol) was diluted in dry DCM (20 mL) and cooled to 0 °C. PBrTo$a stirredsolution of 3, 4, 5-trimethoxybenzyl alcohol (10.0 g, 50.5 mmol) indry dichloromethane (150 mL) under N2 at 5 C was added dropwisea solution of phosphorus tribromide (3.50 mL, 10.1 g, 37.2 mmol) in dichloromethane (10 mL). After stirring at 5 C for45 min, the mixture was poured on to ice (200 g), neutralised withsat. aq. NaHCO3 (120 mL), and the organic layer was separated. Theaqueous phase was extracted with dichloromethane (2 20 mL)and the combined organic phases were washed with brine(30 mL), dried and concentrated to obtain the title compound 31(13.0 g, 99percent) as a colourless solid, m.p. 76–78 C (hexane) [lit.58b86–87 C (petroleum)]; dH (400 MHz, CDCl3) 6.61 (2 H, s, 4-H and6-H), 4.54 (2 H, s, CH2Br), 3.86 (6 H, s, 1-OMe and 3-OMe), 3.84(3 H, s, 2-OMe) (in accord with published data43); dC (100 MHz, CDCl3) 34.4, 56.2, 61.0, 106.2, 133.3, 138.2, 153.4.To a solution of 3, 4, 5-trimethoxybenzyl alcohol 5 (1.0 g, 5.0 mmol, 1.0 equiv) in dry Et4.1.2.2.1 Dissolving 3, 4, 5-trimethoxyl benzyl alcohol (14.05 g, 70.89 mmol) in dichlormethane (100 ml) in a three-necked bottle (250 ml); dissolving phosphorus tribromide (6.73 ml, 70.89 mmol) in dichlormethane (25 ml) for it to react at room temperature for 50 minutes, cooling in refrigeratory, slowly adding deionized water (18 ml, 1.0 mol) dropwise to quench, washing with deionized water (100 ml) twice, drying with anhydrous magnesium sulfate, filtering, washing the filter residue with dichlormethane (20 ml), conflating the filtrate, concentrating in rotarory evaporater, and vacuum drying to get 3, 4, 5-trimethoxyl benzyl bromine (16.05 g of faint yellow solid), yield:84.44percent. Dissolving 3, 4, 5-trimethoxyl benzyl alcohol (ii) (14.05 g, 70.89 mmol) in dichloromethane (100 ml) in a 250 ml three-necked flask; phosphorus tribromide (6.73 ml, 70.89 mmol) in dichloromethane (25 ml) was added dropwise and allowed to react at room temperature for 50 minutes, cooling in ice-bath, slowly adding deionized water (18 ml, 1.0 mol) dropwise to quench the reaction. The organic layer was washed with deionized water (100 ml) twice, drying with anhydrous magnesium sulfate, filtering, washing the filter residue with dichloromethane (20 ml), the combined organic layer concentrated in rotatory evaporater to dry, and was further dried under vacuum to afford 3, 4, 5-trimethoxyl benzyl bromide (16.05 g of faint yellow solid), yield: 84.44percent. The product does not need to be further purified for following reaction. If pure product is wanted, it can be recrystallized to get the white lamellar crystal with a 1:3 mixture of ethyl acetate and n-hexane2. The preparation of 3, 4, 5-trimethoxyl benzyl bromide; Dissolving 3, 4, 5-trimethoxyl benzyl alcohol (14.05 g, 70.89 mmol) in dichlormethane (100 ml) in a 250 ml three-necked flask; phosphorus tribromide (6.73 ml, 70.89 mmol) in dichlormethane (25 ml) was added dropwise and allowed to react at room temperature for 50 minutes, cooling in ice bath, slowly adding deionized water (18 ml, 1.0 mol) dropwise to quench the reaction, washing with deionized water (100 ml) twice, drying with anhydrous magnesium sulfate, filtering, washing the filter residue with dichlormethane (20 ml), the combined organic layer was concentrated in rotatory evaporater to dry, and was further dried under vacuum to afford 3, 4, 5-trimethoxyl benzyl bromide (16.05 g of faint yellow solid), yield 84.44percent.The product does not need to be further purified for following reaction. If pure product is wanted, it can be recrystallized to get the white lamellar crystal with a 1:3 mixture of ethyl acetate and n-hexane.2. Step 2. PBr3 (1.1 equivalents) wasadded dropwise to a solution of 3, 4, 5-trimethoxybenzyl alcohol (1) (2.0 g, 10 mmol) in Et2General procedure: Bromides 16, 17, (+)- and (−)-19, 22 were synthesized from the corresponding monoterpene or methoxyphenyl aldehydes (14, 15, (+)- and (−)-18) via reduction to alcohols with NaBHTo a solution of compound 2 (9.0 g, 45.5 mmol) in dry CHThe following is a general procedure for the in-situ formation of the onium salts, followed by simulated labeling (addition of the nucleophile). To a dry vial was added the imidazole, pyrimidine or benzimidazole precursor (0.1 mmol) and dry dichloromethane (0.2 ml). The vial was capped, and methyl triflate was then added dropwise (12R1, 1.05 eq. ) and the vial was stirred at room temperature overnight. The onium salt was generally soluble under these conditions. A solution of the nucleophile, 2 equivalents, was then added, followed by 10LL of A 1 M solution of 3, 4-dimethoxytoluene (0.01 mmol) in dry THF as internal standard. The vial was placed in a microwave tube and irradiated under continuous cooling for 5-15 minutes at a preselected temperature of 60°C. Upon completion of the procedure, samples were removed and analyzed by GC-MS. The following solutions were used as nucleophiles: KX-K222 complex (X=F, Br, 1) in dry acetonitrile (0. 1 M) for simulating 18F, 76Br and 124I labeling. MeLi (3.0 M in THF) FOR C labeling. The onium salt was prepared substituting tetrahydrofuran for dichloromethane in this latter case. A white microcrystalline precipitate formed, but the reaction proceeded well upon the addition of the methyllithium. The structures for the onium salts prepared from compounds 1, 3, 4a, and 4b (in each case, the counterion was triflate, CF3SO3-) were as follows: OMe Me OMe E, -S Compound 5 N\ OMe (From cpd. 1) Me Compound 6 (From cpd. 3) Me Con s Me Me MeON A-Ph ---N Compound 7 (From cpds. 4a or 4b) Me What follows below in Table 1 is a summary of the reaction conditions leading to the formation of the various onium salts depicted above.The following is a general procedure for the in-situ formation of the onium salts, followed by simulated labeling (addition of the nucleophile). To a dry vial was added the imidazole, pyrimidine or benzimidazole precursor (0.1 mmol) and dry dichloromethane (0.2 ml). The vial was capped, and methyl triflate was then added dropwise (12R1, 1.05 eq. ) and the vial was stirred at room temperature overnight. The onium salt was generally soluble under these conditions. A solution of the nucleophile, 2 equivalents, was then added, followed by 10LL of A 1 M solution of 3, 4-dimethoxytoluene (0.01 mmol) in dry THF as internal standard. The vial was placed in a microwave tube and irradiated under continuous cooling for 5-15 minutes at a preselected temperature of 60°C. Upon completion of the procedure, samples were removed and analyzed by GC-MS. The following solutions were used as nucleophiles: KX-K222 complex (X=F, Br, 1) in dry acetonitrile (0. 1 M) for simulating 18F, 76Br and 124I labeling. MeLi (3.0 M in THF) FOR C labeling. The onium salt was prepared substituting tetrahydrofuran for dichloromethane in this latter case. A white microcrystalline precipitate formed, but the reaction proceeded well upon the addition of the methyllithium. The structures for the onium salts prepared from compounds 1, 3, 4a, and 4b (in each case, the counterion was triflate, CF3SO3-) were as follows: OMe Me OMe E, -S Compound 5 N\ OMe (From cpd. 1) Me Compound 6 (From cpd. 3) Me Con s Me Me MeON A-Ph ---N Compound 7 (From cpds. 4a or 4b) Me What follows below in Table 1 is a summary of the reaction conditions leading to the formation of the various onium salts depicted above.

Molecular Weight:261.11
XLogP3:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:4
Exact Mass:260.00481
Monoisotopic Mass:260.00481
Topological Polar Surface Area:27.7
Heavy Atom Count:14
Complexity:151
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes