Itaconic acid → Rac-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid

HRID 1516622Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][CH:16]=1)[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([NH2:13])=[CH:9][CH:8]=1.[C:17]([OH:25])(=[O:24])[C:18]([CH2:20][C:21](O)=[O:22])=[CH2:19]>C1(C)C=CC=CC=1.C(O)(=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][CH:16]=1)[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]2[C:21](=[O:22])[CH2:20][CH:18]([C:17]([OH:25])=[O:24])[CH2:19]2)=[CH:9][CH:8]=1

Participants

Conditions

Temperature: 101 °C

Procedure

4-(3-Fluoro-benzyloxy)-phenylamine (31.2 g, 144 mmol) was dissolved in toluene (208 mL) and acetic acid (52 mL). Itaconic acid (18.96 g, 144 mmol) was added to the stirred mixture. The mixture was heated to reflux (101° C.) and kept at this temperature for 3 h. On cooling, the product started to crystallize. At 10° C., heptane (125 mL) was added to the suspension which was stirred 1 h at 0° C. and filtered. The crystals were washed with toluene/heptane 1:1 and with heptane and dried in vacuo to afford the crude product (43.2 g). The crude product was purified by treatment with hot isopropyl acetate to give rac-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid (40.5 g, 86%; HPLC: 99.2% area), m.p. 148-149° C. (uncorr.).

Workup

temperatureThe mixture was heated
temperatureOn cooling
customto crystallize
additionAt 10° C., heptane (125 mL) was added to the suspension which
filtrationfiltered
washThe crystals were washed with toluene/heptane 1:1 and with heptane
customdried in vacuo
customto afford the crude product (43.2 g)
customThe crude product was purified by treatment with hot isopropyl acetate

Sources & evidence

ORD record: ord-1b4c1dc0754d4a23aca67755b1affd29
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08227505B2

Reaction notes

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