Lithium diisopropylamide → 1,1,1-Trifluoro-4-(5-fluoro-2-methoxyphenyl)-2-furo[3,2-c]pyridin-2-ylmethyl-4-methylpentan-2-ol

HRID 400687Notes

Reaction equation

HRID 400687 reaction equation
[CH3:1][C:2]1[O:10][C:9]2[CH:8]=[CH:7][N:6]=[CH:5][C:4]=2[CH:3]=1.C([N-]C(C)C)(C)C.[Li+].[F:19][C:20]([F:37])([F:36])[C:21](=[O:35])[CH2:22][C:23]([C:26]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:27]=1[O:33][CH3:34])([CH3:25])[CH3:24]>C1COCC1>[F:37][C:20]([F:19])([F:36])[C:21]([CH2:1][C:2]1[O:10][C:9]2[CH:8]=[CH:7][N:6]=[CH:5][C:4]=2[CH:3]=1)([OH:35])[CH2:22][C:23]([C:26]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:27]=1[O:33][CH3:34])([CH3:25])[CH3:24]

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 100849201,1,1-Trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methylpentan-2-oneHCID 138030642-Methylfuro[3,2-c]pyridine

Product 1

HCID 114640401,1,1-Trifluoro-4-(5-fluoro-2-methoxyphenyl)-2-furo[3,2-c]pyridin-2-ylmethyl-4-methylpentan-2-olYield 45%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 2-methylfuro[3,2-c]pyridine (prepared according to the procedure by T. Kitamura, K. Tsuda, and Y. Fujiwara, Tetrahedron Lett. 1998, 39, pp. 5375-5376) (26.0 mg, 0.195 mmol) in 2 mL of THF was treated with lithium diisopropylamide (LDA; 1.5 M in cyclohexane, 195 μL) dropwise at −78° C. The mixture was stirred for 30 minutes (the color changed from yellow to orange-red) and was slowly treated with a solution of 1,1,1-trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methylpentan-2-one (81.5 mg, 0.293 mmol) in 1 mL of THF. The reaction was stirred at −78° C. for 4.5 hours, quenched with 5 mL of saturated ammonium chloride solution, and diluted with 20 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, 5% to 50% gradient) gave 36.0 mg (45% yield) of the title product as a clear oil.

Workup

  1. stirringThe reaction was stirred at −78° C. for 4.5 hours
  2. customquenched with 5 mL of saturated ammonium chloride solution
  3. additiondiluted with 20 mL of ethyl acetate
  4. customThe phases were separated
  5. extractionthe aqueous layer was extracted with three 10 mL portions of ethyl acetate
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-252989f597004f1bb0be0a1767883854
Source dataset
uspto-grants-2014_06
Patent number
US08741897B2

Reaction notes

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