methyl (2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-2-phenylacetate

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

Procedure: To (R)-methyl 2-(tert-butoxycarbonylamino)-2-phenylacetate (E4) in DMF at −40° C. was added NaH and the solution was warmed to 0° C. for 20 minutes. DMS was added and solution was stirred at room temperature for 3 hours. The mixture was poured into NH4Cl(sat)/HCl (1N) 3:1 and extracted with EtOAc. The organics were dried (Na2SO4), filtered and evaporated to give crude E5. Column chromatography Hexanes/EtOAc gave pure (R)-methyl 2-(tert-butoxycarbonyl(methyl)amino)-2-phenylacetate (E5). extracted with EtOAc The organics were dried (Na2SO4) filtered evaporated

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

Procedure: To (R)-methyl 2-(tert-butoxycarbonylamino)-2-phenylacetate (E4) in DMF at −40° C. was added NaH and the solution was warmed to 0° C. for 20 minutes. DMS was added and solution was stirred at room temperature for 3 hours. The mixture was poured into NH4Cl(sat)/HCl (1N) 3:1 and extracted with EtOAc. The organics were dried (Na2SO4), filtered and evaporated to give crude E5. Column chromatography Hexanes/EtOAc gave pure (R)-methyl 2-(tert-butoxycarbonyl(methyl)amino)-2-phenylacetate (E5). extracted with EtOAc The organics were dried (Na2SO4) filtered evaporated

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

Procedure: To a two-necked 50 mL round bottom flask were added (R)-methyl 2-((tert-butoxycarbonyl)amino)-2-phenylacetate (1.2 g, 5.68 mmol) and dry THF (30 mL). The resulting mixture was cooled to 0° C. Ethyl magnesium bromide (3.02 g, 22.72 mmol) (3M solution in diethyl ether) was added dropwise, and the mixture was slowly allowed to warm to ambient temperature. The mixture was then stirred at ambient temperature for 24 hours. After completion of reaction (monitored by TLC, TLC eluent: 30% EtOAc in hexane), the mixture was quenched in NH4Cl solution and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated to yield 1.2 g (90.0%) of (R)-tert-butyl (2-ethyl-2-hydroxy-1-phenylbutyl)carbamate as a white solid. 1H NMR (300 MHz, CDCl3) δ: 7.35-7.26 (m, 5H), 5.56 (d, J=9.1 Hz, 1H), 4.61 (d, J=9.4 Hz, 1H), 1.68-1.63 (m, 2H), 1.39 (s, 9H), 1.32-1.22 (m, 2H), 0.92 (t, J=7.4 Hz, 3H), 0.80 (t, J=7.4 Hz, 3H). to warm to ambient temperature the mixture was quenched in NH4Cl solution extracted with EtOAc The combined organic layers were dried over Na2SO4 filtered concentrated

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

Procedure: To a two-necked 50 mL round bottom flask were added (R)-methyl 2-((tert-butoxycarbonyl)amino)-2-phenylacetate (1.2 g, 5.68 mmol) and dry THF (30 mL). The resulting mixture was cooled to 0° C. Ethyl magnesium bromide (3.02 g, 22.72 mmol) (3M solution in diethyl ether) was added dropwise, and the mixture was slowly allowed to warm to ambient temperature. The mixture was then stirred at ambient temperature for 24 hours. After completion of reaction (monitored by TLC, TLC eluent: 30% EtOAc in hexane), the mixture was quenched in NH4Cl solution and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated to yield 1.2 g (90.0%) of (R)-tert-butyl (2-ethyl-2-hydroxy-1-phenylbutyl)carbamate as a white solid. 1H NMR (300 MHz, CDCl3) δ: 7.35-7.26 (m, 5H), 5.56 (d, J=9.1 Hz, 1H), 4.61 (d, J=9.4 Hz, 1H), 1.68-1.63 (m, 2H), 1.39 (s, 9H), 1.32-1.22 (m, 2H), 0.92 (t, J=7.4 Hz, 3H), 0.80 (t, J=7.4 Hz, 3H). to warm to ambient temperature the mixture was quenched in NH4Cl solution extracted with EtOAc The combined organic layers were dried over Na2SO4 filtered concentrated

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

Procedure: To (R)-methyl 2-(tert-butoxycarbonylamino)-2-phenylacetate (E4) in DMF at −40° C. was added NaH and the solution was warmed to 0° C. for 20 minutes. DMS was added and solution was stirred at room temperature for 3 hours. The mixture was poured into NH4Cl(sat)/HCl (1N) 3:1 and extracted with EtOAc. The organics were dried (Na2SO4), filtered and evaporated to give crude E5. Column chromatography Hexanes/EtOAc gave pure (R)-methyl 2-(tert-butoxycarbonyl (methyl)amino)-2-phenylacetate (E5). extracted with EtOAc The organics were dried (Na2SO4) filtered evaporated

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

Procedure: To (R)-methyl 2-(tert-butoxycarbonylamino)-2-phenylacetate (E4) in DMF at −40° C. was added NaH and the solution was warmed to 0° C. for 20 minutes. DMS was added and solution was stirred at room temperature for 3 hours. The mixture was poured into NH4Cl(sat)/HCl (1N) 3:1 and extracted with EtOAc. The organics were dried (Na2SO4), filtered and evaporated to give crude E5. Column chromatography Hexanes/EtOAc gave pure (R)-methyl 2-(tert-butoxycarbonyl (methyl)amino)-2-phenylacetate (E5). extracted with EtOAc The organics were dried (Na2SO4) filtered evaporated

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

Procedure: To (R)-methyl 2-(tert-butoxycarbonylamino)-2-phenylacetate (E4) in DMF at −40° C. was added NaH and the solution was warmed to 0° C. for 20 minutes. DMS was added and solution was stirred at room temperature for 3 hours. The mixture was poured into NH4Cl(sat)/HCl (1N) 3:1 and extracted with EtOAc. The organics were dried (Na2SO4), filtered and evaporated to give crude E5. Column chromatography Hexanes/EtOAc gave pure (R)-methyl 2-(tert-butoxycarbonyl(methyl)amino)-2-phenylacetate (E5). extracted with EtOAc The organics were dried (Na2SO4) filtered evaporated

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

Procedure: To a two-necked 50 mL round bottom flask were added (R)-methyl 2-((tert-butoxycarbonyl)amino)-2-phenylacetate (1.2 g, 5.68 mmol) and dry THF (30 mL). The resulting mixture was cooled to 0° C. Ethyl magnesium bromide (3.02 g, 22.72 mmol) (3M solution in diethyl ether) was added dropwise, and the mixture was slowly allowed to warm to ambient temperature. The mixture was then stirred at ambient temperature for 24 hours. After completion of reaction (monitored by TLC, TLC eluent: 30% EtOAc in hexane), the mixture was quenched in NH4Cl solution and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated to yield 1.2 g (90.0%) of (R)-tert-butyl (2-ethyl-2-hydroxy-1-phenylbutyl)carbamate as a white solid. 1H NMR (300 MHz, CDCl3) δ: 7.35-7.26 (m, 5H), 5.56 (d, J=9.1 Hz, 1H), 4.61 (d, J=9.4 Hz, 1H), 1.68-1.63 (m, 2H), 1.39 (s, 9H), 1.32-1.22 (m, 2H), 0.92 (t, J=7.4 Hz, 3H), 0.80 (t, J=7.4 Hz, 3H). to warm to ambient temperature the mixture was quenched in NH4Cl solution extracted with EtOAc The combined organic layers were dried over Na2SO4 filtered concentrated