Lithium diisopropylamide → 2-[2-(4-Chloro-phenyl)-5-methyl-thiazol-4-yl]-5-[(5-fluoro-pyridin-2-yl)-hydroxy-methyl]-3-methoxy-cyclopent-2-enone

HRID 2170813Notes

Reaction equation

HRID 2170813 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+].[F:30][C:31]1[CH:32]=[CH:33][C:34]([CH:37]=[O:38])=[N:35][CH:36]=1>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])[CH:15]([CH:37]([C:34]4[CH:33]=[CH:32][C:31]([F:30])=[CH:36][N:35]=4)[OH:38])[CH2:16][C:17]=3[O:18][CH3:19])[N:12]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 103516975-Fluoropyridine-2-carboxaldehydeHCID 669261702-[2-(4-Chloro-phenyl)-5-methyl-thiazol-4-yl]-3-methoxy-cyclopent-2-enone

Product 1

HCID 669261292-[2-(4-Chloro-phenyl)-5-methyl-thiazol-4-yl]-5-[(5-fluoro-pyridin-2-yl)-hydroxy-methyl]-3-methoxy-cyclopent-2-enoneYield 71.9%

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 (400 mg, 1.25 mmol) in anhydrous tetrahydrofuran (10 ml) at −78° C. under an atmosphere of nitrogen was added lithium diisopropylamide (1.8M in THF/heptanes/ethylbenzene; 0.76 m, 1.37 mmol) dropwise over a period of 5 minutes, and the reaction allowed to stir at 78° C. for 30 minutes. A solution of 5-fluoro-pyridine-2-carbaldehyde (171 mg, 1.37 mmol) in anhydrous tetrahydrofuran (1 ml) was then added dropwise over a period of 5 minutes before the reaction was allowed to warm to room temperature and stirred for a further 30 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]-5-[(5-fluoro-pyridin-2-yl)-hydroxy-methyl]-3-methoxy-cyclopent-2-enone (400 mg).

Workup

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

Sources & evidence

ORD record
ord-fc9b26ca2ac147d4a732f1b33a08a12e
Source dataset
uspto-grants-2015_06
Patent number
US09051300B2

Reaction notes

Loading…