benzyl (2R)-2-hydroxypropanoate

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

Procedure: To a solution of 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenol (2.90 g, 11.4 mmol) and (R)-2-hydroxypropionic acid benzyl ester (2.25 g, 12.5 mmol) in dry THF (100 mls) at 0° C. under nitrogen is added triphenylphosphine followed by dropwise addition of diisopropylazodicarboxylate (3.36 mls, 17 mmol). The resulting yellow mixture is stirred for 1 hr then left the stand for 16 hours. The reaction mixture is partitioned between water and ethyl acetate and the layers separated. The aqueous is further extracted with ethyl acetate and the combined organic layers dried over magnesium sulphate, filtered and the solvent removed under reduced pressure. Column chromatography on silica gel using 10% ethyl acetate/hexane as eluent yielded (S)-2-[4-(5-Trifluoromethyl-pyridin-2-yloxy)-phenoxy]-propionic acid benzyl ester as a colourless oil. In one example 3.25 g are made representing 69% yield and in >99% ee (as determined by nmr). then left the stand for 16 hours The reaction mixture is partitioned between water and ethyl acetate the layers separated The aqueous is further extracted with ethyl acetate the combined organic layers dried over magnesium sulphate filtered the solvent removed under reduced pressure

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

Procedure: To a solution of 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenol (2.90 g, 11.4 mmol) and (R)-2-hydroxypropionic acid benzyl ester (2.25 g, 12.5 mmol) in dry THF (100 mls) at 0° C. under nitrogen is added triphenylphosphine followed by dropwise addition of diisopropylazodicarboxylate (3.36 mls, 17 mmol). The resulting yellow mixture is stirred for 1 hr then left the stand for 16 hours. The reaction mixture is partitioned between water and ethyl acetate and the layers separated. The aqueous is further extracted with ethyl acetate and the combined organic layers dried over magnesium sulphate, filtered and the solvent removed under reduced pressure. Column chromatography on silica gel using 10% ethyl acetate/hexane as eluent yielded (S)-2-[4-(5-Trifluoromethyl-pyridin-2-yloxy)-phenoxy]-propionic acid benzyl ester as a colourless oil. In one example 3.25 g are made representing 69% yield and in >99% ee (as determined by nmr). then left the stand for 16 hours The reaction mixture is partitioned between water and ethyl acetate the layers separated The aqueous is further extracted with ethyl acetate the combined organic layers dried over magnesium sulphate filtered the solvent removed under reduced pressure

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

Procedure: To a solution of 1 g of 4-{(S)-3-tert-Butoxycarbonyl-2-[(4-hydroxy-7-methyl-quinoline-2-carbonyl)-amino]-propionyl}-piperazine-1-carboxylic acid ethyl ester and 350 mg of (R)-2-Hydroxy-propionic acid benzyl ester in 20 ml of THF, 764 mg of Triphenyl-phosphane and 507 mg of Diethyl azodicarboxylate was added and stirred for 2 h. Then, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic phase was dried over MgSO4 and the solvents were removed under reduced pressure. The crude product was purified by chromatography on silica gel eluting with a gradient of n-heptane/ethyl acetate. The fractions containing the product were combined and the solvent evaporated under reduced pressure. Yield: 1.3 g. extracted with ethyl acetate The organic phase was dried over MgSO4 the solvents were removed under reduced pressure The crude product was purified by chromatography on silica gel eluting with a gradient of n-heptane/ethyl acetate The fractions containing the product the solvent evaporated under reduced pressure

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

Procedure: To a solution of 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenol (2.90 g, 11.4 mmol) and (R)-2-hydroxypropionic acid benzyl ester (2.25 g, 12.5 mmol) in dry THF (100 mls) at 0° C. under nitrogen is added triphenylphosphine followed by dropwise addition of diisopropylazodicarboxylate (3.36 mls, 17 mmol). The resulting yellow mixture is stirred for 1 hr then left the stand for 16 hours. The reaction mixture is partitioned between water and ethyl acetate and the layers separated. The aqueous is further extracted with ethyl acetate and the combined organic layers dried over magnesium sulphate, filtered and the solvent removed under reduced pressure. Column chromatography on silica gel using 10% ethyl acetate/hexane as eluent yielded (S)-2-[4-(5-Trifluoromethyl-pyridin-2-yloxy)-phenoxy]-propionic acid benzyl ester as a colourless oil. In one example 3.25 g are made representing 69% yield and in >99% ee (as determined by nmr). then left the stand for 16 hours The reaction mixture is partitioned between water and ethyl acetate the layers separated The aqueous is further extracted with ethyl acetate the combined organic layers dried over magnesium sulphate filtered the solvent removed under reduced pressure