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A mixture of (1S)-4-amino-N-[2-tert-butoxy-5-(trifluoromethyl)benzyl]1-isopropylcyclopent-2-ene-1-carboxamide (35 g, 88 mmol) and diethyl oxomalonate (31 g, 176 mmol) in toluene (350 mL) was refluxed until no more starting material left as judged by HPLC. The reaction mixture was cooled to 0° C. and 1,8-diazabicyclo[5.4.0]undec-7-ene (27 g, 176 mmol) was added. The reaction mixture was then warmed to r.t. and stirred at this temperature for 1 hr before being quenched with 1M HCl and vigorously stirred for 1 hr. The reaction mixture was diluted with EtOAc and the two layers were separated. The aqueous phase was then extracted with EtOAc (5×). The organics were combined, dried over sodium sulfate and evaporated to dryness. The crude was purified by column chromatography on silica gel eluting with hexane:EtOAc (11:1) to yield 32 g of (1S)—N-[2-tert-butoxy-5-(trifluoromethyl)benzyl]-1-isopropyl-4-oxocyclopent-2-ene-1-carboxamide as a pale yellow solid.

1. temperaturewas refluxed until
2. waitleft
3. temperatureThe reaction mixture was then warmed to r.t.
4. custombefore being quenched with 1M HCl
5. stirringvigorously stirred for 1 hr
6. additionThe reaction mixture was diluted with EtOAc
7. customthe two layers were separated
8. extractionThe aqueous phase was then extracted with EtOAc (5×)
9. dry with materialdried over sodium sulfate
10. customevaporated to dryness
11. customThe crude was purified by column chromatography on silica gel eluting with hexane:EtOAc (11:1)