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

HRID 731762Notes

Reaction equation

[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]

Participants

Conditions

Temperature: 0 °C

Procedure

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).

Workup

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

Sources & evidence

ORD record: ord-684062a8ff4c4bceaac3981106855512
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07585882B2

Reaction notes

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