Nitrogen → 2,5-Di-tert-butyl-3-hydroxyisoindolin-1-one

Participants

Reaction Conditions

Reaction Steps

In a 1 L three-necked flask fitted with an addition funnel with line to a bubbler, and a nitrogen inlet, that was purged with N2, N,4-di-tert-butylbenzamide (5 g, 21.4 mmol, Eq: 1.00) was combined with THF (200 ml) to give a light yellow solution. The reaction was cooled to −78° C. The sec-butyllithium in cyclohexanes (31.4 ml of 1.4 M, 43.9 mmol, Eq: 2.05) was added dropwise slowly and with a stream of N2. A yellow solution resulted. The reaction mixture was warmed to −15° C. for 1 h. A pale yellow suspension resulted. The reaction mixture was cooled back down to −78° C. Dry DMF (3.13 g, 3.32 ml, 42.9 mmol, Eq: 2) was added dropwise. The reaction mixture was allowed to warm to room temperature. 30 mL of saturated NH4Cl was added slowly at 0° C. The reaction mixture was poured into 150 mL H2O and extracted with EtOAc (3×250 mL). The combined organic extracts were washed with brine, dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 80 g, 0% to 40% EtOAc in hexanes to afford the desired product (4.9 g, 88% yield). (M+H)+=262 m/e.

Provenance & Evidence