(3R)-4-[(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-[(2-methylpropan-2-yl)oxymethyl]piperazin-2-one

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

Procedure: 97 mg of t-butyl (R)-4-[(R)-2-(t-butoxymethyl)-3-oxopiperazin-1-yl]-4-oxo-1-(2,4,5-trifluorophenyl)butan-2-ylcarbamate prepared in Step 8 was dissolved in 3 mL of methanol, followed by addition of 2 mL of 2N-hydrochloric acid/diethyl ether and stirring at room temperature for 3 hours.

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

Procedure: 65.7 g of benzyl(R)-4-[(R)-2-(t-butoxymethyl)-3-oxopiperazine-1-yl]-4-oxo-1-(2,4,5-trifluorophenyl)butane-2-ylcarbamate of the above Step 1 was dissolved in 409 mL of methanol; a solution in which 13.1 g of palladium/carbon was wetted with 92 ml of ethyl acetate was added; and then stirred for 2 hours under hydrogen pressure of 15 bar. The resulting reaction solution was filtered with diatomite, and then concentrated under reduced pressure to obtain 34.8 g of a title compound. was added The resulting reaction solution was filtered with diatomite concentrated under reduced pressure

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

Procedure: 503 mg of the compound obtained in Example 11 was dissolved in 4 mL of ethyl acetate to which a solution of 183 mg of adipic acid in 3 mL of acetone/water (30/1(v/v)) was then slowly added followed by stirring for 30 min. The reaction mixture was concentrated, to which 2 mL of ethyl acetate and 1 mL of 2-propanol were then added followed by stirring. 15 mL of hexane was added thereto, and resulting mixture was stirred for 10 min and filtered to afford 336 mg of the title compound as a solid. was then slowly added The reaction mixture was concentrated, to which 2 mL of ethyl acetate and 1 mL of 2-propanol were then added by stirring 15 mL of hexane was added resulting mixture was stirred for 10 min filtered

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

Procedure: 498 mg of the compound obtained in Example 11 was dissolved in 3 mL of acetone to which a solution of 147 mg of succinic acid in 2 mL of acetone/water (20/1(v/v)) was then slowly added followed by stirring for 30 min. The reaction mixture was concentrated to dryness under reduced pressure to afford 596 mg of the title compound as a solid. was then slowly added The reaction mixture was concentrated to dryness under reduced pressure

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

Procedure: 498 mg of the compound obtained in Example 11 was dissolved in 4 mL of acetone to which a solution of 166 mg of L-malic acid in 1 mL of acetone was then slowly added followed by stirring for 30 min. The reaction mixture was concentrated, to which 2 mL of ethyl acetate and 1 mL of 2-propanol were then added followed by stirring. 15 mL of hexane was added thereto, and the resulting mixture was stirred for 10 min and filtered to afford 506 mg of the title compound as a solid. was then slowly added The reaction mixture was concentrated, to which 2 mL of ethyl acetate and 1 mL of 2-propanol were then added by stirring 15 mL of hexane was added the resulting mixture was stirred for 10 min filtered

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

Procedure: 500 mg of the compound obtained in Example 11 was dissolved in 3 mL of ethyl acetate to which a solution of 74.5 mg of acetic acid in 1 mL of ethyl acetate was then slowly added followed by stirring for 30 min. The reaction mixture was concentrated, to which 2 mL of ethyl acetate and 1 mL of 2-propanol were then added followed by stirring. 15 mL of hexane was added thereto, and the resulting mixture was stirred for 10 min and filtered to afford 495 mg of the title compound as a solid. was then slowly added The reaction mixture was concentrated, to which 2 mL of ethyl acetate and 1 mL of 2-propanol were then added by stirring 15 mL of hexane was added the resulting mixture was stirred for 10 min filtered

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

Procedure: 501 mg of the compound obtained in Example 11 was dissolved in 3 mL of 2-propanol, to which 84 μl of a 85% phosphoric acid aqueous solution was then slowly added followed by stirring for 30 min. 3 mL of 2-propanol was added thereto, and the resulting mixture was stirred for 10 min and filtered to afford 100 mg of the title compound as a solid. was then slowly added the resulting mixture was stirred for 10 min filtered

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

Procedure: 496 mg of the compound obtained in Example 11 was dissolved in 2 mL of ethanol, to which a solution of 273 mg of anhydrous citric acid in 1 mL of water was then slowly added, followed by stirring for 30 min. The reaction mixture was concentrated, to which 2 mL of ethyl acetate and 1 mL of 2-propanol were then added followed by stirring. 15 mL of hexane was added thereto followed by stirring for 10 min and filtration to afford 637 mg of the title compound as a solid. was then slowly added The reaction mixture was concentrated, to which 2 mL of ethyl acetate and 1 mL of 2-propanol were then added by stirring 15 mL of hexane was added by stirring for 10 min filtration

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

Procedure: 55 mg of the compound obtained in Example 11 was dissolved in 0.56 mL of acetone to which a solution of 26 mg of L-tartaric acid in 0.35 mL of ethanol/water (9/1(v/v)) was then slowly added, followed by stirring for 30 min. 0.56 mL of 2-propanol was added thereto, followed by stirring for 10 min and filtration to afford 77 mg of the title compound as a solid. was then slowly added by stirring for 10 min filtration

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

Procedure: 60 mg of the compound obtained in Example 1 was added to 10 mL of a 5% sodium hydrogen carbonate aqueous solution, and the mixture was extracted two times with 10 mL of a mixed solution of dichloromethane/2-propanol (4/1(v/v)). The organic layer was dried under reduced pressure to afford 55 mg of the title compound as a solid. the mixture was extracted two times with 10 mL of a mixed solution of dichloromethane/2-propanol (4/1(v/v)) The organic layer was dried under reduced pressure