Acetonitrile → (1,3-DIoxoisoindol-2-yl)(4-fluorophenyl)acetic acid

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Reaction Steps

To a stirred solution of 4-fluorophenylglycine (3.38 g, 20.0 mmol) and sodium carbonate in 450 mL of 2:1 water:acetonitrile is added N-carbethoxyphthalimide (4.38 g, 20 mmol). After 1 hour, the reaction mixture is partially concentrated to remove the acetonitrile. The resulting slurry is filtered and the pH of the stirred filtrate is adjusted to 1-2 with 4 N hydrochloric acid and then stirred for an additional 30 minutes and filtered. The solid is air-dried and then dried in vacuo (60° C.,<1 mm) to afford 4.55 g (76%) of α-phthalimido4-fluorophenylacetic acid as a white powder: mp 180-183° C.; 1H NMR (DMSO-d6, 250 MHz)δ 8.10-7.80 (m, 4H), 7.65-7.45 (m, 4H), 7.3-7.10 (t, 2H), 6.10 (s, 1H); 13C NMR (DMSO-d6, 250 MHz) δ 168.9, 166.9, 163.6, 159.7, 135.0, 131.4, 131.3 (m), 130.9, 123.5, 115.0, 114.7, 54.4. Anal. Calculated for C18H10NO4F. Theoretical: C, 64.22; H, 3.37; N, 4.68. Found: C, 64.13; H, 3.33; N, 4.63.

Provenance & Evidence