Lithium diisopropylamide → 2-(4-Benzyloxy-2,6-dimethylphenyl)-3-methoxy-5-[1-(tetrahydropyran-4-yl)-methylidene]cyclopent-2-enone

HRID 1193038Notes

Reaction equation

[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([CH3:15])[C:12]([C:16]2[C:17](=[O:23])[CH2:18][CH2:19][C:20]=2[O:21][CH3:22])=[C:11]([CH3:24])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([N-]C(C)C)(C)C.[Li+].[O:33]1[CH2:38][CH2:37][CH:36]([CH:39]=O)[CH2:35][CH2:34]1.CC(C)([O-])C.[K+]>C1COCC1>[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([CH3:15])[C:12]([C:16]2[C:17](=[O:23])[C:18](=[CH:39][CH:36]3[CH2:37][CH2:38][O:33][CH2:34][CH2:35]3)[CH2:19][C:20]=2[O:21][CH3:22])=[C:11]([CH3:24])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 2-(4-benzyloxy-2,6-dimethylphenyl)-3-methoxycyclopent-2-enone (1.93 g, 6.0 mmol) in THF (25 ml) under a nitrogen atmosphere at −78° C. is added a solution of lithium diisopropylamide (3.33 ml, 6.0 mmol, 1.8M in tetrahydrofuran) dropwise over 1 minute. The reaction is then stirred at −78° C. for 30 minutes followed by the addition of 4-tetrahydropyran carbaldehyde (0.684 g, 6.0 mmol) in one portion. After a further 5 minutes at −78° C. the reaction is allowed to warm to ambient temperature and stir for an additional 1 hour. Potassium tert-butoxide (1.10 g, 9.82 mmol) is then added in one portion and the reaction mixture is allowed to stir for a further 1 hour at room temperature. After quenching with saturated ammonium chloride solution (50 ml) the crude product is extracted into ethyl acetate (50 ml), and the organic phase is dried over anhydrous magnesium sulfate and concentrated in vacuo. Purification by flash column chromatography affords 2-(4-benzyloxy-2,6-dimethylphenyl)-3-methoxy-5-[1-(tetrahydropyran-4-yl)-methylidene]cyclopent-2-enone as a white solid.

Workup

waitAfter a further 5 minutes at −78° C. the reaction is allowed
temperatureto warm to ambient temperature
stirringstir for an additional 1 hour
stirringto stir for a further 1 hour at room temperature
customAfter quenching with saturated ammonium chloride solution (50 ml) the crude product
extractionis extracted into ethyl acetate (50 ml)
dry with materialthe organic phase is dried over anhydrous magnesium sulfate
concentrationconcentrated in vacuo
customPurification by flash column chromatography

Sources & evidence

ORD record: ord-152421b166b0419bb7930cdcbb2cb909
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08680339B2

Reaction notes

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