Rolipram → 1-(2,3-Difluorobenzyl)-4-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyrrolidone

HRID 641168

Reaktionsgleichung

Reaktionsgleichung von HRID 641168
[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH:15]3[CH2:19][NH:18][C:17](=[O:20])[CH2:16]3)[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[F:23][C:24]1[C:31]([F:32])=[CH:30][CH:29]=[CH:28][C:25]=1[CH2:26]Br.C(OCC)(=O)C>CN(C)C=O.C1OCCOCCOCCOCCOC1.O1CCCC1>[F:23][C:24]1[C:31]([F:32])=[CH:30][CH:29]=[CH:28][C:25]=1[CH2:26][N:18]1[CH2:19][CH:15]([C:9]2[CH:10]=[CH:11][C:12]([O:13][CH3:14])=[C:7]([O:6][CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)[CH:8]=2)[CH2:16][C:17]1=[O:20]

Komponenten

8

Edukt 4

HCID 5092RolipramHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 5179841-(Bromomethyl)-2,3-difluoro-benzene

Produkt 1

HCID 236146471-(2,3-Difluorobenzyl)-4-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyrrolidoneAusbeute 70 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 3633615-Crown-5Lösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

4-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyrrolidone (110 mg, 0.4 mmol) in 2 ml of N,N-dimethylformamide and 110 μl of 15-crown-5 is treated with sodium hydride (20 mg, 0.5 mmol) under nitrogen at ambient temperature. After 3 hours, the mixture is cooled to 0° C. and treated with 2,3-difluorobenzyl bromide (166 mg, 0.8 mmol) in 2 ml of tetrahydrofuran. The resulting mixture is allowed to stir at ambient temperature for 6 hours. 100 ml of ethyl acetate is added, followed by 100 ml of ice cold water. After usual aqueous work up, the crude product is purified by flash column chromatography (ethyl acetate/hexane 2:1) to give 112 mg (70%) of 1-(2,3-difluorobenzyl)-4-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyrrolidone: 1H NMR (300 MHz, CDCl3) δ 7.18-6.98 (m, 3H), 6.79 (d, J=8.1 Hz, 1H), 6.90 (d, J=8.1 Hz, 1H), 6.68 (s, 1H) 4.71-4.69 (m, 1H), 4.60 (s, 2H), 3.81 (s, 3H), 3.68 (t, J=9.0 Hz, 1H), 3.66-3.54 (m, 1H), 3.29 (dd, J=9.6, 7.2 Hz, 1H), 2.84 (dd, J=16.8, 9.0 Hz, 1H), 2.57 (dd, J=16.8, 8.4 Hz, 1H), 2.00-1.75 (b, 6H), 1.70-1.52 (b, 2H).

Aufarbeitung

  1. customAfter usual aqueous work up, the crude product is purified by flash column chromatography (ethyl acetate/hexane 2:1)

Quellen und Nachweise

ORD-Eintrag
ord-ec93857298334ccb876a88b3cb8e8086
Quelldatensatz
uspto-grants-2010_04
Patentnummer
US07696198B2

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