Methyl (3R)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-(2,4,5-trifluorophenyl)butanoate

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

Procedure: To a solution of (R)-Methyl-3-[N-(tert-butoxycarbonyl)amino]-4-(2,4,5-tri-fluorophenyl)butanoate of Example 4 (1.28 g, 3.69 mmol) in 15 mL THF and 15 mL water was added 3 equiv. LiOH.H2O. The reaction mixture was stirred for 16 h. 10 ml saturated NaHCO3 was added. THF was evaporated and the aq solution was acidified to pH 2-3 with NaHSO4, then extracted by ethyl acetate (3×15 mL). The combined organic phase was washed with brine and dried over Na2SO4. Concentration in vacuo afforded 1.17 g of white solid (95.1%). 1H NMR (300 MHz, CD3OD) 7.13-7.03 (m, 2H), 4.20-4.10 (m, 1H), 3.00-2.90 (m, 1H), 2.75-2.60 (m, 1H), 2.45-2.55 (m, 2H), 1.35 (s, 9H) THF was evaporated extracted by ethyl acetate (3×15 mL) The combined organic phase was washed with brine dried over Na2SO4 Concentration in vacuo

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

Procedure: 1.28 g (3.71 mmol) of (Z)-Methyl-3-[N-(tert-butoxycarbonyl)amino]-4-(2,4,5-trifluorophenyl)but-2-enoate of Example 3, 2.2 mg TangPhosRh(COD)BF4 and 10 mL THF were charged to a pressure bomb under N2 atmosphere. The N2 atmosphere was replaced by H2 (10 bars). The mixture was stirred at rt for 18 h. The reaction solution was passed through a silica gel pad and evaporated to dryness. The reaction gave quantitative yield and 99.0% ee. 1H NMR (300 MHz, CDCl3) 7.10-7.00 (m, 1H), 6.95-6.85 (m, 1H), 5.10 (m, 1H), 4.20-4.10 (m, 1H), 3.70 (s, 3H), 2.85 (m, 1H), 2.60-2.50 (m, 1H), 1.39 (s, 9H) evaporated to dryness The reaction gave quantitative yield and 99.0% ee

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 53 mg of (R)-methyl 3-(t-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoate, 1.5 mL of tetrahydrofuran, and 0.5 mL of water were added to 25 mL flask and the resulting reaction solution was cooled to 0° C. 7.32 mg of lithium hydroxide was added to the reaction solution and stirred for 6 hours while the reaction temperature was naturally increased to room temperature. After completing the reaction, 5 mL of ethyl acetate and 5 mL of water were added to the reaction solution and stirred for 10 minutes. An aqueous layer was isolated, cooled at 0° C., and 2 N hydrochloric acid aqueous solution was dropped to adjust to pH 3-4. The aqueous layer was extracted with methylene chloride:methanol=10:1 solvent, dehydrated with magnesium sulfate, and then concentrated under reduced pressure to obtain 40.8 mg of a title compound. the resulting reaction solution was naturally increased to room temperature were added to the reaction solution stirred for 10 minutes An aqueous layer was isolated cooled at 0° C. The aqueous layer was extracted with methylene chloride concentrated under reduced pressure

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a clean flask, 34.73 g (R)-methyl 3-(tert-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butyrate, 100 ml toluene, 160 ml water and 4.8 g sodium hydroxide were added. The mixture was warmed to 60° C. and kept at this temperature for 3 hours. 4.73 g hydrochloric acid was added dropwisely. After completion, the resulting mixture was kept at 20-30° C. for 2 hours and filtrated to obtain 30.66 g (R)-3-(tert-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)n-butyric acid (yield: 92%). After completion, the resulting mixture was kept at 20-30° C. for 2 hours filtrated