ethyl 2-[3-(bromomethyl)phenoxy]acetate

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 (2R)-2-(4,5-diphenyloxazol-2-yl)pyrrolidine (400 mg) and 3-bromomethyl-1-ethoxycarbonylmethoxybenzene (0.76 g) in N,N-dimethylformamide (10 ml) was added K2CO3 (1 g) at room temperature. The mixture was stirred for 2 hours at the same temperature and then partitioned between ethyl acetate and water. The organic layer was washed with water, sat. NaHCO3, and brine. The dried solvent was evaporated in vacuo and the residue was purified by chromatography on silica gel to give (2R)-2-(4,5-diphenyloxazol-2-yl)-1(3-ethoxycarbonylmethoxybenzyl)pyrrolidine (0.27 g). partitioned between ethyl acetate and water The organic layer was washed with water, sat. NaHCO3, and brine The dried solvent was evaporated in vacuo the residue was purified by chromatography on silica gel

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

Procedure: To a solution of 3-hydroxymethyl-1-ethoxycarbonylmethoxybenzene (1 g) in dichloromethane (10 ml) was added BBr3 (0.45 ml). After 1 hour, the solvent was evaporated in vacuo and the residue was dissolved in ethyl acetate. The organic layer was washed with NaHCO3 and brine. The dried solvent was evaporated in vacuo to give 3-bromomethyl-1-ethoxycarbonylmethoxybenzene (0.76 g). the solvent was evaporated in vacuo the residue was dissolved in ethyl acetate The organic layer was washed with NaHCO3 and brine The dried solvent was evaporated in vacuo

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

Procedure: A solution containing ethyl 3-(hydroxymethyl)phenoxyacetate (2.6 g.) and carbon tetrabromide (8.3 g.) in DMF (30 ml.) was treated with a solution of triphenylphosphine (6.55 g.) in DMF (20 ml.) with stirring. The temperature was maintained below 15° C. during the addition using an ice bath. After 1 hour the mixture was poured into ice-water (300 ml.) and the aqueous mixture was extracted with ether (3×100 ml.). The combined extracts were washed with water (3×100 ml.) and saturated brine (100 ml.), dried (MgSO4) and concentrated. The resultant oil was purified by flash column chromatography, eluting with petrol (60°-80° )/ether (80:20 v/v) to give ethyl 3 (bromomethyl)phenoxyacetate (2.4 g.) as a colourless oil, NMR: 1.3 (3H,t), 4.25 (2H,q), 4.4 (2H,s), 4.6 (2H,s) and 6.7-7.4 (4H,m)ppm. The temperature was maintained below 15° C. during the addition the aqueous mixture was extracted with ether (3×100 ml.) The combined extracts were washed with water (3×100 ml.) and saturated brine (100 ml.) dried (MgSO4) concentrated The resultant oil was purified by flash column chromatography eluting with petrol (60°-80° )/ether (80:20 v/v)

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

Procedure: To a mixture of (2R, 4R)-2-(4,5-diphenyloxazol-2-yl)pyrrolidin-4-ol (229 mg) and potassium carbonate (155 mg) in DMF (5 mL) was added ethyl 3-(bromomethyl)phenoxyacetate (245 mg) at 5° C. and stirred at the same temperature for 30 minutes then at room temperature for 16 hours. The reaction mixture was diluted with EtOAc, washed with water and brine, dried (MgSO4), and evaporated in vacuo. The residue was purified by silica gel column chromatography (hexane-EtOAc, 1:2) to give ethyl 3-{[(2R, 4R)-2-(4,5-diphenyloxazol-2-yl)-4-hydroxypyrrolidin-1-yl]methyl}phenoxyacetate (359.7 mg). at room temperature for 16 hours washed with water and brine dried (MgSO4) evaporated in vacuo The residue was purified by silica gel column chromatography (hexane-EtOAc, 1:2)

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

Procedure: To a mixture of (2R, 4R)-2-(4,5-diphenyloxazol-2-yl)pyrrolidin-4-ol (229 mg) and potassium carbonate (155 mg) in DMF (5 mL) was added ethyl 3-(bromomethyl)phenoxyacetate (245 mg) at 5° C. and stirred at the same temperature for 30 minutes then at room temperature for 16 hours. The reaction mixture was diluted with EtOAc, washed with water and brine, dried (MgSO4), and evaporated in vacuo. The residue was purified by silica gel column chromatography (hexane-EtOAc, 1:2) to give ethyl 3-{[(2R, 4R)-2-(4,5-diphenyloxazol-2-yl)-4-hydroxypyrrolidin-1-yl]methyl}phenoxyacetate (359.7 mg). at room temperature for 16 hours washed with water and brine dried (MgSO4) evaporated in vacuo The residue was purified by silica gel column chromatography (hexane-EtOAc, 1:2)

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

Procedure: To a solution of (2R)-2-(4,5-diphenyloxazol-2-yl)pyrrolidine (400 mg) and 3-bromomethyl-1-ethoxycarbonylmethoxybenzene (0.76 g) in N,N-dimethylformamide (10 ml) was added K2CO3 (1 g) at room temperature. The mixture was stirred for 2 hours at the same temperature and then partitioned between ethyl acetate and water. The organic layer was washed with water, sat. NaHCO3, and brine. The dried solvent was evaporated in vacuo and the residue was purified by chromatography on silica gel to give (2R)-2-(4,5-diphenyloxazol-2-yl)-1(3-ethoxycarbonylmethoxybenzyl)pyrrolidine (0.27 g). partitioned between ethyl acetate and water The organic layer was washed with water, sat. NaHCO3, and brine The dried solvent was evaporated in vacuo the residue was purified by chromatography on silica gel

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

Procedure: To a solution of (2R)-2-(4,5-diphenyloxazol-2-yl)pyrrolidine (400 mg) and 3-bromomethyl-1-ethoxycarbonylmethoxybenzene (0.76 g) in N,N-dimethylformamide (10 ml) was added K2CO3 (1 g) at room temperature. The mixture was stirred for 2 hours at the same temperature and then partitioned between ethyl acetate and water. The organic layer was washed with water, sat. NaHCO3, and brine. The dried solvent was evaporated in vacuo and the residue was purified by chromatography on silica gel to give (2R)-2-(4,5-diphenyloxazol-2-yl)-1(3-ethoxycarbonylmethoxybenzyl)pyrrolidine (0.27 g). partitioned between ethyl acetate and water The organic layer was washed with water, sat. NaHCO3, and brine The dried solvent was evaporated in vacuo the residue was purified by chromatography on silica gel

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

Procedure: To a solution of 3-hydroxymethyl-1-ethoxycarbonylmethoxybenzene (1 g) in dichloromethane (10 ml) was added BBr3 (0.45 ml). After 1 hour, the solvent was evaporated in vacuo and the residue was dissolved in ethyl acetate. The organic layer was washed with NaHCO3 and brine. The dried solvent was evaporated in vacuo to give 3-bromomethyl-1-ethoxycarbonylmethoxybenzene (0.76 g). the solvent was evaporated in vacuo the residue was dissolved in ethyl acetate The organic layer was washed with NaHCO3 and brine The dried solvent was evaporated in vacuo