Lithium diisopropylamide → 2-[2-(4-Chloro-phenyl)-5-methyl-thiazol-4-yl]-3-methoxy-5-[1-(tetrahydro-pyran-4-yl)-meth-(E)-ylidene]-cyclopent-2-enone

HRID 2170810Notes

Reaction equation

HRID 2170810 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]([CH3:21])=[C:11]([C:13]3[C:14](=[O:20])[CH2:15][CH2:16][C:17]=3[O:18][CH3:19])[N:12]=2)=[CH:4][CH:3]=1.C([N-]C(C)C)(C)C.[Li+].[O:30]1[CH2:35][CH2:34][CH:33]([CH:36]=O)[CH2:32][CH2:31]1.CC(C)([O-])C.[K+]>O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]([CH3:21])=[C:11]([C:13]3[C:14](=[O:20])/[C:15](=[CH:36]/[CH:33]4[CH2:34][CH2:35][O:30][CH2:31][CH2:32]4)/[CH2:16][C:17]=3[O:18][CH3:19])[N:12]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 2724682Lithium diisopropylamideHCID 9964078Tetrahydro-2H-pyran-4-carboxaldehydeHCID 23665647Potassium tert-butoxideHCID 669261702-[2-(4-Chloro-phenyl)-5-methyl-thiazol-4-yl]-3-methoxy-cyclopent-2-enone

Product 1

HCID 669261932-[2-(4-Chloro-phenyl)-5-methyl-thiazol-4-yl]-3-methoxy-5-[1-(tetrahydro-pyran-4-yl)-meth-(E)-ylidene]-cyclopent-2-enoneYield 23.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
78 °C

Procedure

To a solution of 2-[2-(4-Chloro-phenyl)-5-methyl-thiazol-4-yl]-3-methoxy-cyclopent-2-enone (640 mg, 2 mmol) in anhydrous tetrahydrofuran (12 ml) at −78° C. under an atmosphere of nitrogen was added lithium diisopropylamide (1.8M in THF/heptanes/ethylbenzene; 1.1 ml, 2 mmol) dropwise over a period of 5 minutes, and the reaction allowed to stir at 78° C. for 30 minutes. A solution of tetrahydro-pyran-4-carbaldehyde (228 mg, 2 mmol) in anhydrous tetrahydrofuran (1 ml) was then added dropwise over a period of 5 minutes before the reaction is allowed to warm to room temperature and stirred for a further 30 minutes. Potassium tert-butoxide (337 mg, 3 mmol) was then added in one portion and the reaction stirred for a further 90 minutes. The reaction was quenched by the addition of saturated aqueous ammonium chloride solution (50 ml) and extracted with ethyl acetate (50 ml) and the organic later separated, dry loaded onto silica and purified by flash chromatography to give 2-[2-(4-Chloro-phenyl)-5-methyl-thiazol-4-yl]-3-methoxy-5-[1-(tetrahydro-pyran-4-yl)-meth-(E)-ylidene]-cyclopent-2-enone (195 mg).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for a further 30 minutes
  3. stirringthe reaction stirred for a further 90 minutes
  4. customThe reaction was quenched by the addition of saturated aqueous ammonium chloride solution (50 ml)
  5. extractionextracted with ethyl acetate (50 ml)
  6. customthe organic later separated
  7. customdry loaded onto silica
  8. custompurified by flash chromatography

Sources & evidence

ORD record
ord-e90724bc21464f6795a5b57d1574bb3f
Source dataset
uspto-grants-2015_06
Patent number
US09051300B2

Reaction notes

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