These common heterocyclic compound, 3339-73-9, name is 3-(1,3-Dioxoisoindolin-2-yl)propanoic acid, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. Safety of 3-(1,3-Dioxoisoindolin-2-yl)propanoic acid
Step-1: 3-(1,3-dioxoisoindolin-2-yl)-N’-(2-methoxyacetyl)propanehydrazide Oxalyl chloride (27.47 g, 0.216 mol) was added slowly to an ice-cooled solution of 3-(1,3-dioxoisoindolin-2-yl)propanoic acid (15.80 g, 0.072 mol) in DCM (250 mL) followed by catalytic DMF (0.5 mL). The reaction mixture was stirred at room temperature for 1 h and volatiles were removed completely under vacuum to obtain the intermediate acid chloride as a yellow solid. A solution of 2-methoxyacetohydrazide (2, 9.01 g, 0.086 mol) in DCM (50 mL) was added to a solution of this acid chloride in DCM (200 mL) at 0 C. followed by triethylamine (60.5 g, 0.597 mol). The resultant reaction mixture was stirred at room temperature for 1 h. The resulting yellow suspension was quenched onto crushed ice (200 mL). Separated organic layer was washed with water (2×200 mL), brine (150 mL) and concentrated under vacuum to afford crude product (5 g). The aqueous layer which also contains desired product was concentrated under reduced pressure to afford a solid residue. The crude residue was dried and extracted sequentially with THF (1000 mL), acetone (300 mL) and acetonitrile (400 mL). The combined organic layer was concentrated to obtain yellow semisolid (37 g) which was combined with solid residue (5 g) from organic layer and was used in the next reaction without purification. LC-MS [M+H]+ 306.1 m/z.
The synthetic route of 3-(1,3-Dioxoisoindolin-2-yl)propanoic acid has been constantly updated, and we look forward to future research findings.
Reference:
Patent; PROTEOSTASIS TEHRAPEUTICS, INC.; Bastos, Cecilia M.; Munoz, Benito; Tait, Bradley; (48 pag.)US2017/1993; (2017); A1;,
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