Task 1

Benzyl ((1S,2S,3'S,5S)-1'-methoxy-2',9-dioxo-6-oxaspiro[bicyclo[3.2.2]nonane-4,3'-indolin]-2- yl)carbamate (23)

To a stirred solution of 22 (994 mg, 3.00 mmol) in CH₂Cl₂ ¹ (15 mL) at 0 °C was added oxalyl chloride² (1.0 mL, 12 mmol). After stirring at room temperature for 1 h, solvent was removed by rotary evaporation ³ to give the crude carboxylic acid chloride as white foam. The residue was dissolved in toluene ⁴ (15 mL) and NaN₃ ⁵(780 mg, 12.0 mmol) in H₂O (15 mL) was added to the mixture at 0 °C. After 10 min, the reaction mixture was partitioned between EtOAc ⁶(20 mL) and H₂O (10 mL). The aqueous phase was extracted with EtOAc (20 mL) twice. The combined organic extract
was washed⁷ with brine⁸ (10 mL), dried over MgSO₄, filtered and concentrated in vacuo ⁹to afford the crude acyl azide. The crude mixture was dissolved in toluene (15 mL) and benzyl alcohol¹⁰ (930 ìL, 9.0 mmol) was added. The mixture was heated at 80 °C for 30 min and the reaction mixture was partitioned between EtOAc (20 mL) and H₂O (15 mL). The aqueous phase was extracted with EtOAc (20 mL) once and the combined organic extract was washed with brine (10 mL), dried over MgSO₄, filtered and concentrated in vacuo to afford the crude Cbz amine. The residue was purified by flash column chromatography on silica gel (n-hexane/EtOAc = 1/0 to 2/1) to afford 23 (1.08 g, 2.47 mmol, 82%) as a pale yellow foam.

IR (neat, cm^–1) 3336, 2939, 2359, 1736, 1706, 1617, 1523, 1230; ¹H NMR (CDCl₃, 400 MHz) δ 7.44 (d, J =7.3 Hz, 1H), 7.40–7.27 (m, 6H), 7.14 (dd, J = 7.6, 7.6 Hz, 1H), 7.00 (d, J = 7.8 Hz, 1H), 6.77 (d, J =8.7 Hz, 1H), 5.11 (d, J = 12.4 Hz, 1H), 5.07 (d, J = 12.4 Hz, 1H), 4.54 (m, 1H), 4.36 (d, J = 10.5 Hz,1H), 4.13 (dd, J = 10.5, 3.2 Hz, 1H), 3.99 (s, 3H), 3.77 (s, 1H), 2.99 (d, J = 19.7 Hz, 1H), 2.88 (m,1H), 2.57 (dd, J = 15.6, 6.4 Hz, 1H), 2.46 (dd, J = 15.6, 5.5 Hz, 1H), 1.91 (dd, J = 15.6, 4.1 Hz, 1H).

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Footnotes:

^{1.[It is highly soluble in water. It is extremely toxic.] back}

^2.[]back

^{3. [efficient technique that removes large amounts of solvents from solutions by evaporation]}

^back

^{4. []↩}

^{5.[Sodium azide is the inorganic compound. This colourless azide salt is is used for the preparation of other azide compounds.}

^{It is highly soluble in water. It is extremely toxic.] back}

^{6.[Ethyl Acetate.]back}

^{7. [Washing removes impurities in a sep funnel]back}

^{8. [A saturated aqueous NaCl solution that is used to draw the aqueous parts (water) out from an organic solution.]back}

^{9.[under a vacuum, ie: vacuum filtration]}

^back

^10.[

^{Benzyl Alcohol:}

^{a colorless liquid with a mild pleasant aromatic odor.}

^{It is a useful solvent due to its polarity, low toxicity, and low vapor pressure]back}