Lithium Hexamethyldisilazide → 1-[(5-Chloro-3-methyl-1-benzothien-2-yl)sulfonyl]-4-[3-(trifluoromethyl)pyridin-2-yl]piperazin-2-one

HRID 1868115Notes

Reaction equation

HRID 1868115 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[C:4]([N:9]2[CH2:14][CH2:13][NH:12][C:11](=[O:15])[CH2:10]2)=[N:5][CH:6]=[CH:7][CH:8]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Cl:28][C:29]1[CH:30]=[CH:31][C:32]2[S:36][C:35]([S:37](Cl)(=[O:39])=[O:38])=[C:34]([CH3:41])[C:33]=2[CH:42]=1>C1COCC1>[Cl:28][C:29]1[CH:30]=[CH:31][C:32]2[S:36][C:35]([S:37]([N:12]3[CH2:13][CH2:14][N:9]([C:4]4[C:3]([C:2]([F:1])([F:16])[F:17])=[CH:8][CH:7]=[CH:6][N:5]=4)[CH2:10][C:11]3=[O:15])(=[O:39])=[O:38])=[C:34]([CH3:41])[C:33]=2[CH:42]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 27357565-Chloro-3-methylbenzo(b)thiophene-2-sulfonyl chlorideHCID 471744384-(3-(Trifluoromethyl)pyridin-2-yl)piperazin-2-one

Product 1

HCID 685535541-[(5-Chloro-3-methyl-1-benzothien-2-yl)sulfonyl]-4-[3-(trifluoromethyl)pyridin-2-yl]piperazin-2-oneYield 3.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of 4-(3-(trifluoromethyl)pyridin-2-yl)piperazin-2-one (150 mg, 0.61 mmol) in anhydrous THF (2.0 mL) was cooled to −78° C., followed by drop-wise addition of LHMDS (0.92 mL, 0.92 mmol (1.0 Min THF)). The reaction was allowed to stir five minutes after which a solution of 5-chloro-3-methyl-2-benzothiophene sulfonyl chloride in anhydrous THF (221 mg, 0.79 mmol in 1 mL) was added drop-wise. The reaction mixture was allowed to stir at −78° C. for approximately two hours, after which it was judged complete by TLC. The reaction was quenched with excess H2O (10 mL), extracted into ethyl acetate (3×10 mL), and finally washed with aqueous NaHCO3 (2×10 mL). The organic layers were combined and dried over Na2SO4, decanted, and concentrated in vacuo. The resultant crude oil was purified via normal phase SiO2 column chromatography using a 5%-20% EA/Hex solvent gradient. The desired product, was isolated in >95% purity, 3.5% yield (10 mg).

Workup

  1. additionwas added drop-wise
  2. customThe reaction was quenched with excess H2O (10 mL)
  3. extractionextracted into ethyl acetate (3×10 mL)
  4. washfinally washed with aqueous NaHCO3 (2×10 mL)
  5. dry with materialdried over Na2SO4
  6. customdecanted
  7. concentrationconcentrated in vacuo
  8. customThe resultant crude oil was purified via normal phase SiO2 column chromatography

Sources & evidence

ORD record
ord-8ccb530e62704804b0f1c82a9a0758a7
Source dataset
uspto-grants-2009_12
Patent number
US07632838B2

Reaction notes

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