3-(BROMOMETHYL)PHENOL

Intermediate 17: 3-(Bromomethyl) phenolTo a 50 mL RB flask fitted with magnetic stirrer was charged 15 mL of dichloromethane. To the stirred solvent was added 3-hydroxymethyl-phenol (0.5 g, 4.03 mmol). The RM was brought to 0 and phosphorous t ribromide (1.6 g, 0.56 mL, 6.04 mmol) was added drop wise. After addition, the RM was stirred at RT for 1 h. After 1 h, the RM was diluted with dichloromethane (25 mL) arid the organic layer was washed with water (20 mL). The organic layer was dried over anhydrous NaTo a suspension of 3-hydroxybenzylalcohol (1.0 g, 8.06 mmol) and PPhCBrSynthesis of [lR- [la (Z), 2p (R*), 3a, 5a]]-7- [3, 5-dihydroxy-2- (3-hydroxy-5-phenylpentyl) cyclopentyl]-5-heptenoic acid 3- (nitrooxymethyl) phenyl ester (compound 4); 1. Preparation of 3- [ (Bromo) methyl] phenol; 3-[(Hydroxy) methyl] phenol was dissolved in acetonitrile (300 ml) and dichloromethane (900ml) and the resulting mixture was poured in the flask kept under argon; magnetic stirring was set on. The solution was then cooled with an ice. bath and carbon tetrabromide and triphenilphosphine were added. The latter. was added in small portions in order to maintain the temperature at 2-3 °C. The solution was stirred for 1 hour at 2-3°C and then for an additional hour at room temperature. After this period the reaction (checked by TLC, using EtOAc/Petroleum ether 3/7 as the eluent) was complete. The mixture was evaporated under reduce pressure and 500 ml of petroleum ether and 500 ml of EtOAc were added to the resulting yellow thick oil in a. 21 round flask. A pitchy solid was formed. The mixture was kept under stirring at room temperature overnight and subsequently filtered and concentrated under reduce pressure, furnishing ca. 50 g of an oily residue. The oil was purified by flash chromatography over 600g of silica gel, using EtOAc/Petroleum ether 2/8 as the eluent. Further purification was achieved by crystallising the resulting bromide from petroleum ether. A white solid was obtained (24 g, 64percent). Analysis TLC : (EtOAc/Petroleum ether 3/7) Rf =0.4 HPLC purity: > 98percent FT-IR (KBr, cm1) : 3252, 1589, 1479, 1392, 1270, 1208, 1155, 952, 880, 791, 741, 686.3-[(hydroxyl)methyl]phenol (25.0 g, 200 mmol) was dissolved in acetonitrile (300 ml) and dichloromethane (900ml) and the resulting mixture was poured in the flask kept under argon; magnetic stirring was set on. The solution was then cooled with an ice bath and carbon tetrabromide (80.0 g , 240 mmol, 1.2 eq) and triphenylphosphine (77.0 g, 290 mmol, 1.5 eq) were added.The latter was added in small portions in order to maintain the temperature at 2-3°C.The solution was stirred for 1 hour at 2-3°C and then for an additional hour at room temperature. After period the reaction conversion was complete. The obtained mixture was evaporated under reduce pressure and 500 ml of petroleum ether and 500 ml of ethyl acetate were added to the resulting yellow thick oil in a round flask. A pitchy solid was formed. The mixture was kept under stirring at room temperature overnight and subsequently filtered and concentrated under reduce pressure, furnishing ca. 50 g of an oily residue.The oil was purified by flash chromatography over silica gel using ethyl acetate/petroleum ether as eluent. Further purification was achieved by crystallising the resulting bromide from petroleum ether. A white solid was obtained (24 g, 64percent) .TLC (EtOAc/Petroleum ether 3/7) Rf=0.4 HPLC purity>98percentFT-IR (KBr, cm'Example 4. Preparation of 3-f f nitroxy)methyl1phenol 3-[(Hydroxy)methyl]phenol (25 g, 0.2 mol), is dissolved in acetonitrile (300 ml) and dichloromethane (900 ml) and the resulting mixture is poured into a flask kept under argon with stirring. The solution is cooled with an ice bath and carbon tetrabromide and triphenylphosphine are added. The latter was added in small portions in order to maintain the temperature at ca. 2-3 C. The solution is stirred for 1 hour at 2-3 C followed by an additional hour at room temperature. The reaction conversion is checked by TLC, using EtOAc/Petroleum ether 3/7 as the eluent) until complete. The obtained mixture is evaporated under reduced pressure and 500 ml of petroleum ether and 500 ml of EtOAc is added to the resulting yellow thick oil in a 21 round flask. The mixture is stirred at room temperature overnight and subsequently filtered and concentrated under reduce pressure, furnishing ca. 50 g of an oily residue. The oil is purified by flash chromatography over 600 g of silica gel, using EtOAc/Petroleum ether 2/8 as the eluent. Further purification is achieved by crystallizing the resulting bromide from petroleum ether. A white solid is obtained (24 g, 64percent). HPLC purity: >98percent; FT-IR (KBr, cmExample 40 Synthesis of 3-hydroxybenzyl bromideA reactor was charged with 3-hydroxybenzyl alcohol (500 mg), and dichloromethane (5 ml) and the mixture cooled to -15 °C. Phosphorous tribromide (568 μΚ) was added dropwise and the reaction was allowed to warm to room temperature over 3 hours. The reaction was quenched by the dropwise addition of water (10 ml) and the organics were separated. The aqueous was washed with dichloromethane (2x10 ml) and the combined organics were washed with saturated aqueous sodium bicarbonate solution (10 ml), then water (10 ml). The organics were dried (Na2S04), filtered and reduced to yield an oil, which was purified on a Reveleris® X2 Flash Chromatography System, eluting with n-hexane and ethyl acetate. Appropriate fractions were collected for the product peak and were reduced by rotary evaporation to obtain the desired product as a white solid (446 mg, 59percent). The structure was confirmed as 3-hydroxybenzyl bromide by 1H NMR.To a solution of 3-(hydroxymethyl)phenol (2.5 g, 20.1 mmol) in dry DCM (50 mL) was added PBr

Molecular Weight:187.03
XLogP3:1.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:185.96803
Monoisotopic Mass:185.96803
Topological Polar Surface Area:20.2
Heavy Atom Count:9
Complexity:85
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes