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

HRID 1938174노트

반응식

HRID 1938174 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-3439060cf5cf4959bc9992ad25999ada
출처 데이터셋
uspto-grants-1997_12
특허 번호
US05693639

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