ditert-butyl 4-amino-4-[3-[(2-methylpropan-2-yl)oxy]-3-oxopropyl]heptanedioate

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

Procedure: To 5 ml CH2Cl2 was added 1 g of triester 62 (2.4 mmol, 1 equiv) and 0.3 g triethylamine (2.9 mmol, 1.2 equiv.) The solution was cooled to 0° C. with an ice bath and 0.23 g acetyl chloride (2.9 mmol, 1.2 equiv) was added dropwise. The solution was stirred for a further 4 hours and allowed to warm slowly to room temperature. The solution was poured into a separating funnel and washed with 2×15 ml HCl (5% aqueous) and 1×15 ml concentrated NaCl. The solution was dried over Na2SO4 and the solvent was removed in vacuo. The residue was dissolved in minimal EtOAc and loaded onto a silica column, where it was purified by column chromatography with EtOAc and hexane (1:1) to give 0.79 g of a white solid in 72% yield. to warm slowly to room temperature The solution was poured into a separating funnel washed with 2×15 ml HCl (5% aqueous) and 1×15 ml concentrated NaCl The solution was dried over Na2SO4 the solvent was removed in vacuo The residue was dissolved in minimal EtOAc was purified by column chromatography with EtOAc and hexane (1:1)

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

Procedure: To a solution of di-tert-butyl 4-amino-4-(3-(tert-butoxy)-3-oxopropyl)heptanedioate (5.00 g, 12.0 mmol) and 2-bromoacetyl bromide (1.46 mL, 3.40 g, 16.80 mmol) in DCM (60 mL) was added Et3N (2.5 mL) at room temperature. The reaction mixtures were stirred at room temperature for overnight. The reaction mixtures were diluted with DCM (300 mL), washed with 1N HCl solution, and dried over Na2SO4. Solvent was evaporated under reduce pressure to afford a residue, which was purified by biotage eluting with 10% EtOC in hexanes to 100% EtOAc to afford di-tert-butyl 4-(2-bromoacetamido)-4-(3-(tert-butoxy)-3-oxopropyl)heptanedioate (2.58 g, 40%). 1H NMR (400 MHz, CDCl3) 6.43 (s, 1H), 3.76 (s, 2H), 2.20 (t, J=8.0 Hz, 2H), 1.98 (t, J=8.0 Hz, 6H), 1.43 (s, 27H); MS (ESI), 558, 560 (M+Na)+. The reaction mixtures The reaction mixtures washed with 1N HCl solution dried over Na2SO4 Solvent was evaporated to afford a residue, which was purified by biotage eluting with 10% EtOC in hexanes to 100% EtOAc

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

Procedure: To a solution of amine 72 (513 mg, 1.23 mmol) in CH2Cl2 (6.2 mL) was added succinic anhydride (135 mg, 1.35 mmol) and DMAP (8 mg, 0.062 mmol). The mixture was stirred for 6 h 15 min and concentrated to dryness. The crude product was purified by flash chromatography on a Biotage™ flash chromatography system, using a gradient of 50-100% EtOAc in CH2Cl2 as eluent to yield acid 73 (407 mg, 64%) as a white foam: 1H NMR (400 MHz, CDCl3) δ 1.44 (s, 27H), 1.97-2.01 (m, 6H), 2.23-2.26 (m, 6H), 2.47-2.51 (m, 2H), 2.65-2.68 (m, 2H), 6.83 (s, 1H). concentrated to dryness The crude product was purified by flash chromatography on a Biotage™ flash chromatography system