Above text is from the experimental procedure for the intramolecular amide bond formation. If this reaction were to be scaled up for an industrial process, identify two different aspects of this procedure which would not be appropriate on industrial scale. (2 marks)

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The crude material was dissolved in DMF (120) mL) and HOAt (2.05 g, 15.1 mmol, 6.0 equiv) was added. To this solution was added DCM (2.4 L, 20/1 DCM/DMF, 1.0 mM) followed by EDC-HC1 (1.44 g. 7.53 mmol, 3.0 equiv). After stirring at room temperature for 12 hours, the reaction mixture was concentrated to ca. 500 mL., aqueous HC1 (1 M, 1500 mL) was added and the layers were separated. The aqueous phase was extracted with DCM (4 x 250 mL) and the combined extracts were washed with brine (2 x 500 mL), dried over MgSO,, filtered and concentrated. The crude material was purified by flash column chromatography (0/1- 5/4 EtOAc/hexanes) to provide the desired macrocycle 11 (1.34 g, 64%, light yellow solid), along with the undesired 12 (0.12 g. 6%, yellow film). The crude material was dissolved in DMF (120) mL) and HOAt (2.05 g, 15.1 mmol, 6.0 equiv) was added. To this solution was added DCM (2.4 L, 20/1 DCM/DMF, 1.0 mM) followed by EDC-HC1 (1.44 g. 7.53 mmol, 3.0 equiv). After stirring at room temperature for 12 hours, the reaction mixture was concentrated to ca. 500 mL., aqueous HC1 (1 M, 1500 mL) was added and the layers were separated. The aqueous phase was extracted with DCM (4 x 250 mL) and the combined extracts were washed with brine (2 x 500 mL), dried over MgSO,, filtered and concentrated. The crude material was purified by flash column chromatography (0/1- 5/4 EtOAc/hexanes) to provide the desired macrocycle 11 (1.34 g, 64%, light yellow solid), along with the undesired 12 (0.12 g. 6%, yellow film).

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Answer 1 One aspect of this procedure that would not be appropriate on an industrial scale is the use of a column chrom atography pur ification step T... View the full answer