Thieno(3,2-c)pyridine → 4-(5-Chloro-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-thieno[3,2-c]pyridin-2-ylmethylpentan-2-ol

HRID 400688Notes

Reaction equation

HRID 400688 reaction equation
[S:1]1[C:9]2[CH:8]=[CH:7][N:6]=[CH:5][C:4]=2[CH:3]=[CH:2]1.[Li]CCCC.[Cl:15][C:16]1[CH:17]=[C:18]([C:25]([CH3:35])([CH3:34])[CH2:26][C:27]2([C:30]([F:33])([F:32])[F:31])[CH2:29][O:28]2)[C:19]2[O:23][CH2:22][CH2:21][C:20]=2[CH:24]=1>C1COCC1>[Cl:15][C:16]1[CH:17]=[C:18]([C:25]([CH3:35])([CH3:34])[CH2:26][C:27]([CH2:29][C:2]2[S:1][C:9]3[CH:8]=[CH:7][N:6]=[CH:5][C:4]=3[CH:3]=2)([OH:28])[C:30]([F:31])([F:32])[F:33])[C:19]2[O:23][CH2:22][CH2:21][C:20]=2[CH:24]=1

Participants

5

Reactant 3

HCID 67500Thieno(3,2-c)pyridineHCID 600263575-Chloro-7-[1,1-dimethyl-2-(2-trifluoromethyloxiranyl)ethyl]-2,3-dihydrobenzofuranHCID 178418339Butyllithium

Product 1

HCID 114962304-(5-Chloro-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-thieno[3,2-c]pyridin-2-ylmethylpentan-2-olYield 13%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of thieno[3,2-c]pyridine (prepared according to the procedure by J. H. Wikel, M. L. Denney, and R. T. J. Vasileff, Heterocyclic Chem. 1993, 30, pp. 289-290) (152 mg, 1.12 mmol) in 2 mL of THF was treated with 450 μL of n-BuLi (2.5 M in hexanes) in a dropwise manner at −78° C. The resulting dark reaction mixture was stirred for 30 minutes and treated with a solution of 5-chloro-7-[1,1-dimethyl-2-(2-trifluoromethyloxiranyl)ethyl]-2,3-dihydrobenzofuran (180 mg, 0.561 mmol) in 0.5 mL of THF. The reaction was allowed to warm to room temperature overnight and quenched with a mixture of 5 mL of saturated ammonium chloride solution and 10 mL of ethyl acetate. The phases were separated and the aqueous layer was extracted with three 10 mL portions of ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, and concentrated in vacuo. Flash chromatography (ethyl acetate-hexanes, 20%-30% gradient) gave 33.5 mg (13% yield) of the title product as yellow foam.

Workup

  1. customThe resulting dark reaction mixture
  2. customquenched with a mixture of 5 mL of saturated ammonium chloride solution and 10 mL of ethyl acetate
  3. customThe phases were separated
  4. extractionthe aqueous layer was extracted with three 10 mL portions of ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-afd3f4a06a3d434691e300612efabcbf
Source dataset
uspto-grants-2014_06
Patent number
US08741897B2

Reaction notes

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