2-O-tert-butyl 3-O-ethyl 2-azabicyclo[2.2.1]heptane-2,3-dicarboxylate

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Isopropylmagnesium chloride (41.3 mL of a 2 M solution in THF, 82.6 mmol) was added dropwise to a cooled 0° C. mixture of N,O-dimethylhydroxylamine hydrochloride (4.0 g, 41.3 mmol) and 2-tert-butyl 3-ethyl 2-azabicyclo[2.2.1]heptane-2,3-dicarboxylate (prepared according to procedures described in EP 947506) (7.9 g, 29.5 mmol) in THF (50 mL). The mixture was stirred for 30 min and quenched with saturated aqueous ammonium chloride (50 mL) and 33% aqueous ammonia (50 mL). The mixture was extracted into ethyl acetate (2×100 mL). The combined organic extracts were dried (Na2SO4) and concentrated. The residue was purified on silica gel eluting with iso-hexane on a gradient of ethyl acetate (0-60%) to give the title product (6.17 g, 73%). 1H NMR (400 MHz, CDCl3, δ 1:1 mixture of rotamers): δ 4.37 (0.5H, s), 4.24 (0.5H, s), 4.13 (0.5H, s), 4.06 (0.5H, s), 3.78-3.71 (3H, m), 3.21-3.19 (3H, m), 2.58 (1H, m), 2.10-2.00 (1H, m), 1.80-1.40 (4H, m), 1.44 (4.5H, s) and 1.39 (4.5H, m), 1.19 (1H, m). quenched with saturated aqueous ammonium chloride (50 mL) and 33% aqueous ammonia (50 mL) The mixture was extracted into ethyl acetate (2×100 mL) The combined organic extracts were dried (Na2SO4) concentrated The residue was purified on silica gel eluting with iso-hexane on a gradient of ethyl acetate (0-60%)