8-[(2-methylpropan-2-yl)oxy]-8-oxooctanoic acid

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

Procedure: Octanedioic acid mono-tert-butyl ester (3.14 g, 13.63 mmol) was dissolved in THF (100 mL). TSTU (4.9 g, 16.3 mmol) was added and pH was adjusted to 8.5 with DIPEA (2.85 mL).

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

Procedure: Octanedioic acid mono-tert-butyl ester (3.14 g, 13.63 mmol) was dissolved in THF (100 mL). TSTU (4.9 g, 16.3 mmol) was added and pH was adjusted to 8.5 with DIPEA (2.85 mL).

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

Procedure: A solution of (S)-2-((benzyloxy)carbonyl)amino)-8-(tert-butoxy)-8-oxooctanoic acid (prepared as described in WO2006/061638), EDC.HCl (1.3 eq.), HOBt (1.3 eq.) in DMF (0.3 M) was stirred at room temperature for 10 min. Then F2 and DIPEA (3.0 eq.) were added and the resulting mixture was stirred at room temperature for 1 h 30 min. The reaction mixture was diluted with EtOAc, washed with sat. aq. NaHCO3 sol., brine, dried (Na2SO4), filtered and concentrated under reduced pressure to give a crude that was purified by column chromatography (eluent: Petroleum ether/EtOAc from 97:3 to 3:7) to give the title compound as yellow oil. MS (ES+) C32H39N3O7: 578 (M+H)+. washed with sat. aq. NaHCO3 sol., brine dried (Na2SO4) filtered concentrated under reduced pressure to give a crude that was purified by column chromatography (eluent: Petroleum ether/EtOAc from 97:3 to 3:7)

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

Procedure: A solution of (S)-2-((benzyloxy)carbonyl)amino)-8-(tert-butoxy)-8-oxooctanoic acid (prepared as described in WO2006/061638), EDC.HCl (1.3 eq.), HOBt (1.3 eq.) in DMF (0.3 M) was stirred at room temperature for 10 min. Then F2 and DIPEA (3.0 eq.) were added and the resulting mixture was stirred at room temperature for 1 h 30 min. The reaction mixture was diluted with EtOAc, washed with sat. aq. NaHCO3 sol., brine, dried (Na2SO4), filtered and concentrated under reduced pressure to give a crude that was purified by column chromatography (eluent: Petroleum ether/EtOAc from 97:3 to 3:7) to give the title compound as yellow oil. MS (ES+) C32H39N3O7: 578 (M+H)+. washed with sat. aq. NaHCO3 sol., brine dried (Na2SO4) filtered concentrated under reduced pressure to give a crude that was purified by column chromatography (eluent: Petroleum ether/EtOAc from 97:3 to 3:7)

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

Procedure: Octanedioic acid mono-tert-butyl ester (3.14 g, 13.63 mmol) was dissolved in THF (100 mL). TSTU (4.9 g, 16.3 mmol) was added and pH was adjusted to 8.5 with DIPEA (2.85 mL).

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

Procedure: Octanedioic acid mono-tert-butyl ester (3.14 g, 13.63 mmol) was dissolved in THF (100 mL). TSTU (4.9 g, 16.3 mmol) was added and pH was adjusted to 8.5 with DIPEA (2.85 mL).