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

HRID 2170819Notes

Reaction equation

HRID 2170819 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]([CH2:21][CH3:22])=[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:31]1[CH2:36][CH2:35][CH:34]([CH:37]=[O:38])[CH2:33][CH2:32]1>O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]([CH2:21][CH3:22])=[C:11]([C:13]3[C:14](=[O:20])[CH:15]([CH:37]([OH:38])[CH:34]4[CH2:35][CH2:36][O:31][CH2:32][CH2:33]4)[CH2:16][C:17]=3[O:18][CH3:19])[N:12]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 9964078Tetrahydro-2H-pyran-4-carboxaldehydeHCID 669261362-[2-(4-Chloro-phenyl)-5-ethyl-thiazol-4-yl]-3-methoxy-cyclopent-2-enone

Product 1

HCID 669262142-[2-(4-Chloro-phenyl)-5-ethyl-thiazol-4-yl]-5-[hydroxy-(tetrahydro-pyran-4-yl)-methyl]-3-methoxy-cyclopent-2-enoneYield 36.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
78 °C

Procedure

To a solution of 2-[2-(4-Chloro-phenyl)-5-ethyl-thiazol-4-yl]-3-methoxy-cyclopent-2-enone (175 mg, 0.52 mmol) in anhydrous tetrahydrofuran (5 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 1 minute and the reaction allowed to stir at 78° C. for 40 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 30 seconds 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 layer separated, dry loaded onto silica and purified by flash chromatography to give 2-[2-(4-Chloro-phenyl)-5-ethyl-thiazol-4-yl]-5-[hydroxy-(tetrahydro-pyran-4-yl)-methyl]-3-methoxy-cyclopent-2-enone (86 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 layer separated
  6. customdry loaded onto silica
  7. custompurified by flash chromatography

Sources & evidence

ORD record
ord-fbc5ad9f717040df9ed636a1ba85d9d2
Source dataset
uspto-grants-2015_06
Patent number
US09051300B2

Reaction notes

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