Lithium diisopropylamide → HCID 66926137, compound

HRID 2170824Notes

Reaction equation

HRID 2170824 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([CH3:13])=[C:10]([C:14]3[C:15](=[O:21])[CH2:16][CH2:17][C:18]=3[O:19][CH3:20])[CH:9]=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:37])[CH2:32][CH2:31]1>O1CCCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([CH3:13])=[C:10]([C:14]3[C:15](=[O:21])[CH:16]([CH:36]([OH:37])[CH:33]4[CH2:34][CH2:35][O:30][CH2:31][CH2:32]4)[CH2:17][C:18]=3[O:19][CH3:20])[CH:9]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 9964078Tetrahydro-2H-pyran-4-carboxaldehydeHCID 66926146HCID 66926146, compound

Product 1

HCID 66926137HCID 66926137, compoundYield 84.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
78 °C

Procedure

To a solution of 2-[5-(4-Chloro-phenyl)-2-methyl-thiophen-3-yl]-3-methoxy-cyclopent-2-enone (255 mg, 0.8 mmol) in anhydrous tetrahydrofuran (6 ml) at −78° C. under an atmosphere of nitrogen was added lithium diisopropylamide (1.8M in THF/heptanes/ethylbenzene; 0.49 ml, 0.89 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 (102 mg, 0.89 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-[5-(4-Chloro-phenyl)-2-methyl-thiophen-3-yl]-5-[hydroxy-(tetrahydro-pyran-4-yl)-methyl]-3-methoxy-cyclopent-2-enone (292 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-943b735e37374ca0becc850441850f63
Source dataset
uspto-grants-2015_06
Patent number
US09051300B2

Reaction notes

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