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

HRID 731762

Reaktionsgleichung

Reaktionsgleichung von HRID 731762
[H-].[Na+].[CH:3]1([O:8][C:9]2[CH:10]=[C:11]([CH:17]3[CH2:21][NH:20][C:19](=[O:22])[CH2:18]3)[CH:12]=[CH:13][C:14]=2[O:15][CH3:16])[CH2:7][CH2:6][CH2:5][CH2:4]1.C1OCCOCCOCCOCCOC1.[F:38][C:39]1[C:46]([F:47])=[CH:45][CH:44]=[CH:43][C:40]=1[CH2:41]Br>CN(C)C=O.O1CCCC1.C(OCC)(=O)C>[F:38][C:39]1[C:46]([F:47])=[CH:45][CH:44]=[CH:43][C:40]=1[CH2:41][N:20]1[CH2:21][CH:17]([C:11]2[CH:12]=[CH:13][C:14]([O:15][CH3:16])=[C:9]([O:8][CH:3]3[CH2:4][CH2:5][CH2:6][CH2:7]3)[CH:10]=2)[CH2:18][C:19]1=[O:22]

Komponenten

8

Edukt 4

HCID 5092RolipramHCID 24758Sodium hydrideHCID 3633615-Crown-5HCID 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 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Sodium hydride (20 mg, 0.5 mmol) was added, under an atmosphere of nitrogen at room temperature, to a mixture of 4-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyrrolidone (110 mg, 0.4 mmol) and 110 μL of 15-crown-5 in 2 mL of N,N-dimethylformamide. After 3 hours, the mixture was cooled to 0° C. and 2,3-difluorobenzyl bromide (166 mg, 0.8 mmol) in 2 mL of tetrahydrofuran was added. The resulting mixture was allowed to stir at room temperature for 6 hours. 100 mL of ethyl acetate was added, followed by the addition of 100 mL of ice cold water. After standard aqueous work up, the crude product was purified by flash column chromatography (ethyl acetate/hexane 2:1) to afford 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 standard aqueous work up, the crude product was purified by flash column chromatography (ethyl acetate/hexane 2:1)

Quellen und Nachweise

ORD-Eintrag
ord-684062a8ff4c4bceaac3981106855512
Quelldatensatz
uspto-grants-2009_09
Patentnummer
US07585882B2

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