Diisopropylamine → 4,4,4-Trifluoro-3-hydroxy-3-methyl-1-[4-(pyrid-4-ylsulfonyl)phenyl]but-1-yne

HRID 35888

Reaction equation

HRID 35888 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[N:13]1[CH:18]=[CH:17][C:16]([S:19]([C:22]2[CH:27]=[CH:26][C:25]([C:28]#[CH:29])=[CH:24][CH:23]=2)(=[O:21])=[O:20])=[CH:15][CH:14]=1.[F:30][C:31]([F:36])([F:35])[C:32]([CH3:34])=[O:33]>O1CCCC1>[F:30][C:31]([F:36])([F:35])[C:32]([OH:33])([CH3:34])[C:29]#[C:28][C:25]1[CH:26]=[CH:27][C:22]([S:19]([C:16]2[CH:15]=[CH:14][N:13]=[CH:18][CH:17]=2)(=[O:20])=[O:21])=[CH:23][CH:24]=1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 9871Methyl trifluoromethyl ketoneHCID 199393044-(4-Pyridylsulfonyl)phenylacetyleneHCID 178418339Butyllithium

Product 1

HCID 199393154,4,4-Trifluoro-3-hydroxy-3-methyl-1-[4-(pyrid-4-ylsulfonyl)phenyl]but-1-yneYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

To a solution of diisopropylamine (0.37 mL, 2.66 mmol) in tetrahydrofuran (11 mL) at -20° C. was added n-butyllithium (0.9 mL of 2.5M solution in hexanes, 2.25 mmol) and the resulting solution was stirred for 25 minutes at -20° C. before being cooled to -78° C. To this was added a solution of 4-(4-pyridylsulfonyl)phenylacetylene (0.5 g, 2.05 mmol) in tetrahydrofuran (3 mL) over a five minute period. The mixture was stirred for an additional 15 minutes at -78° C. To this was added 1,1,1-trifluoroacetone (0.20 mL, 2.25 mmol) in one portion. After stirring the mixture at -78° C. for 20 minutes, it was quenched with water, warmed to ambient temperature and the pH adjusted to 7.0 with saturated aqueous NH4Cl . The solution was evaporated and the resulting residue was partitioned between water and ethyl acetate. The ethyl acetate layer was separated, washed (brine), dried and evaporated. The resulting brown oil was purified by chromatography, with ethyl acetate:dichloromethane as the eluent (1:5), to give the title compound as a white solid (0.36 g, 50%); mp 122°-125° C.; NMR (CDCl3): 1.73 (s,3, CH3), 3.37 (s,1, OH), 7.61 (d,2, J=8.2, At), 7.76 (d,2, J=5.1, Ar), 7.93 (d,2, J=4); MS: m/z=356(M+ 1). Analysis for C16H12F3NO3S: Calculated: C, 54.08; H, 3.40; N, 3.94; Found: C, 53.99; H, 3.41; N, 3.75.

Workup

  1. temperaturebefore being cooled to -78° C
  2. stirringThe mixture was stirred for an additional 15 minutes at -78° C
  3. stirringAfter stirring the mixture at -78° C. for 20 minutes
  4. customit was quenched with water
  5. temperaturewarmed to ambient temperature
  6. customThe solution was evaporated
  7. customthe resulting residue was partitioned between water and ethyl acetate
  8. customThe ethyl acetate layer was separated
  9. washwashed (brine)
  10. customdried
  11. customevaporated
  12. customThe resulting brown oil was purified by chromatography, with ethyl acetate

Sources & evidence

ORD record
ord-405c890f059a4932b2e20042fe5d7ff7
Source dataset
uspto-grants-1995_05
Patent number
US05411973

Linked notes

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