C([Mg]Cl)(C)C.[O:6]1[CH2:10][CH2:9][CH2:8][CH2:7]1.[CH3:11][C:12]([CH3:24])([CH3:23])[C:13]([NH:15][C:16]1[CH:21]=CC=C(Br)[N:17]=1)=[O:14].C1(C)C=CC=CC=1.CN(C)C=O>C(O)(=O)C>[CH3:11][C:12]([CH3:24])([CH3:23])[C:13]([NH:15][C:16]1[CH:21]=[CH:7][CH:8]=[C:9]([CH:10]=[O:6])[N:17]=1)=[O:14]
A solution of 2.1 M isopropylmagnesium chloride in tetrahydrofuran (555.3 g, 1.20 mol) was added over 1.5 hours to the crude solution of 2-(trimethylacetylamino)-6-bromopyridine in toluene (501.2 g of crude solution from previous step, 0.500 mol) maintaining the temperature below 3° C. The resulting mixture was aged at 5° C. for 24 hours. Dimethylformamide (112.3 g, 1.54 mol) was added over 20 min maintaining the temperature at 11-15° C. After 15 min, the solution was transferred into 1 L of 10% aqueous acetic acid and the biphasic mixture stirred for 30 min. The organic phase was separated and combined with 500 mL of 20 wt % aqueous sodium hydrogen sulfite. The biphasic mixture was stirred vigorously for 45 min. The aqueous layer was separated and treated with 500 mL of 20 wt % aqueous Na2CO3, then extracted with ethyl acetate (2×500 mL). The combined organic layers were concentrated to approximately 400 mL at 50° C., 600 mmHg. The concentrate was dried over 8 g of MgSO4 and filtered to give 363.7 g of yellow solution (25.65 wt % title aldehyde, 93.28 assay g).
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