Methyl trifluoromethyl ketone → 4,4,4-Trifluoro-3-hydroxy-3-methyl-1-[4-(1-pyrrolidinylsulfonyl)phenyl]but-1-yne

HRID 1938174Notes

Reaction equation

HRID 1938174 reaction equation
[N:1]1([S:6]([C:9]2[CH:14]=[CH:13][C:12]([C:15]#[CH:16])=[CH:11][CH:10]=2)(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.C([Li])CCC.[F:22][C:23]([F:28])([F:27])[C:24](=[O:26])[CH3:25]>O1CCCC1>[F:22][C:23]([F:28])([F:27])[C:24]([OH:26])([CH3:25])[C:16]#[C:15][C:12]1[CH:13]=[CH:14][C:9]([S:6]([N:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)(=[O:7])=[O:8])=[CH:10][CH:11]=1

Participants

5

Reactant 3

HCID 9871Methyl trifluoromethyl ketoneHCID 214691194-(1-Pyrrolidinylsulfonyl)phenylacetyleneHCID 178418339Butyllithium

Product 1

HCID 214691154,4,4-Trifluoro-3-hydroxy-3-methyl-1-[4-(1-pyrrolidinylsulfonyl)phenyl]but-1-yne

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the 4-(1-pyrrolidinylsulfonyl)phenylacetylene (1.3 g) in anhydrous tetrahydrofuran (60 mL) cooled to -78° C. under a nitrogen atmosphere was added n-butyllithium (2.43 mL of a 2.5M solution in hexanes, 6.09 mmol). The anion was generated over a ten minute period at -78° C. To the anion was added a cooled (0° C.) solution of trifluoroacetone (644 mL) in anhydrous tetrahydrrofuran (10 mL) over a 20 second period. The reaction was stirred at -78° C. for five minutes before the ice bath was removed. After an additional five minutes, the reaction was quenched with 2N HCl (50 mL). The product was extracted into diethyl ether. The combined organic extracts were dried, filtered, and evaporated under reduced pressure. The crude product was purified by chromatography (1:3 acetone: hexanes) followed by recrystallization (1:1 diethyl ether:hexanes) to yield the title compound as a white solid (1.38 g); mp 167.8°-168.7° C.; MS: m/z=348(M+1); NMR (CDCl3): 1.74 (s,3), 1.71-1.78 (m,4), 3.15 (s,1), 3.21-3.26.(m,4), 7.56-7.59 (m,2), 7.77-7.80 (m,2). Analysis for C15H16F3NO3S: Calculated: C, 51.87; H, 4.64; N, 4.03; Found: C, 51.80; H, 4.67; N, 3.88.

Workup

  1. waitThe anion was generated over a ten minute period at -78° C
  2. additionTo the anion was added
  3. customwas removed
  4. customthe reaction was quenched with 2N HCl (50 mL)
  5. extractionThe product was extracted into diethyl ether
  6. customThe combined organic extracts were dried
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customThe crude product was purified by chromatography (1:3 acetone: hexanes)
  10. customfollowed by recrystallization (1:1 diethyl ether:hexanes)

Sources & evidence

ORD record
ord-3439060cf5cf4959bc9992ad25999ada
Source dataset
uspto-grants-1997_12
Patent number
US05693639

Reaction notes

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