4-Fluorobenzyl bromide → 5-(4-Fluoro-benzyl)-3-methoxy-2-(2,4,6-trimethyl-phenyl)-cyclopent-2-enone

HRID 1631884Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH2:7][CH2:6][C:5](=[O:8])[C:4]=1[C:9]1[C:14]([CH3:15])=[CH:13][C:12]([CH3:16])=[CH:11][C:10]=1[CH3:17].C(NC(C)C)(C)C.[Li].O1CCCC1.CCCCCCC.C(C1C=CC=CC=1)C.[F:46][C:47]1[CH:54]=[CH:53][C:50]([CH2:51]Br)=[CH:49][CH:48]=1>C1COCC1>[F:46][C:47]1[CH:54]=[CH:53][C:50]([CH2:51][CH:6]2[C:5](=[O:8])[C:4]([C:9]3[C:14]([CH3:15])=[CH:13][C:12]([CH3:16])=[CH:11][C:10]=3[CH3:17])=[C:3]([O:2][CH3:1])[CH2:7]2)=[CH:49][CH:48]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 3-methoxy-2-(2,4,6-trimethyl-phenyl)-cyclopent-2-enone (200 mg, 0.86 mmol) in THF (3 ml) under N2 at −78° C. is added, dropwise, a 1.8 M solution of lithium diisopropylamine in tetrahydrofuran/heptane/ethylbenzene (0.53 ml, 0.95 mmol). The resulting solution is allowed to stir at −78° C. for 40 minutes. A solution of 4-fluorobenzyl bromide (0.16 ml, 1.3 mmol) in THF (1 ml) is then added in one portion, the reaction mixture is stirred at −78° C. for 30 minutes before being allowed to warm to room temperature over a period of 60 minutes. The reaction is quenched by the addition of saturated aqueous ammonium chloride (5 ml) and extracted with ethyl acetate (2×10 ml). The combined organics are purified by flash chromatography to give 5-(4-fluoro-benzyl)-3-methoxy-2-(2,4,6-trimethyl-phenyl)-cyclopent-2-enone (236 mg).

Workup

stirringthe reaction mixture is stirred at −78° C. for 30 minutes
temperatureto warm to room temperature over a period of 60 minutes
customThe reaction is quenched by the addition of saturated aqueous ammonium chloride (5 ml)
extractionextracted with ethyl acetate (2×10 ml)
customThe combined organics are purified by flash chromatography

Sources & evidence

ORD record: ord-2a7c442e51a24797a2cb9e58c3aa610a
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08791303B2

Reaction notes

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