Diisopropylamine → HCID 20456494, compound

Participants

Reaction Conditions

Reaction Steps

A dry, nitrogen purged flask was charged with 1.875 mL 1.6 N (3.0 mole) n-butyl lithium in hexane. The solution was stirred under nitrogen and chilled to -45° to -40° C., and 1.5 L THF (dried over molecular sieve 4 A) was added slowly. Diisopropylamine (303.6 g; 3.0 mole) was added at such a rate that the temperature did not exceed -30° C. Then 307.3 g (3.3 mole) 2-picoline was added with stirring, keeping the temperature below -30° C. The cooling was interrupted, and the mixture was slowly warmed to 10° C. by which time the conversion to anion was complete and all the 2-picolyl lithium had redissolved. The solution was recooled to -45° to -40° C. (the orange solid reprecipitated), and a solution of 285.3 g (1.0 mole) methyl N-p-anisoylanthranilate (III) in 1.9 L THF was added at a rate so the temperature did not exceed -30° C. After the addition, the mixture was slowly warmed to 25° C. The solution was adjusted to pH 6 with 500 mL acetic acid; 5.0 L H2O was added with stirring. Then the organic solvents were distilled in vacuo and the residual yellow semi-solid product was extracted with CH2Cl2 (1×2.5 L). The extract was washed with H2O (1×1.0 L) and stripped to dryness in vacuo. The residue was dissolved in 6.7 L boiling isopropanol. The solution was chilled with stirring to 5°±5° C., and the resulting yellow solid was collected on a filter, rinsed with isopropanol and dried in vacuo at 80° C. for six hours. The filtrate was concentrated and chilled to yield a second crop of product. Both crops of intensely yellow material exhibited single spots in the TLC (7.5 cm silica gel with indicator, 9 CH2Cl2 :1 methanol, UV). The total yield was 306.7 g (88.5%) of material, m.p. 145°-148.5° C.

Provenance & Evidence