(Trifluoromethyl)trimethylsilane → HCID 53496382, compound

HRID 1868120Notes

Reaction equation

HRID 1868120 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([S:14]([C:17]3[CH:18]=[C:19]([C:23](=[O:25])[CH3:24])[CH:20]=[CH:21][CH:22]=3)(=[O:16])=[O:15])[C@H:10]([CH3:26])[CH2:9]2)=[C:4]([C:27]([F:30])([F:29])[F:28])[CH:3]=1.[Si]([C:35]([F:38])([F:37])[F:36])(C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C([O-])(O)=O.[Na+]>[F:36][C:35]([F:38])([F:37])[C:23]([C:19]1[CH:20]=[CH:21][CH:22]=[C:17]([S:14]([N:11]2[CH2:12][CH2:13][N:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=3[C:27]([F:30])([F:29])[F:28])[CH2:9][C@H:10]2[CH3:26])(=[O:16])=[O:15])[CH:18]=1)([OH:25])[CH3:24]

Participants

5

Reactant 3

HCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium FluorideHCID 53496381HCID 53496381, compound

Product 1

HCID 53496382HCID 53496382, compoundYield 64.4%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (3R)-1-[4-fluoro-2-(trifluoromethyl)phenyl]-3-methylpiperazine (2.5 g, 9.53 mmol) in DCM (50 mL) at 0° C. was added 3-acetyl benzenelsulfonyl chloride (2.08 g, 9.53 mmol) and DIPEA (3.32 mL, 19.06 mmol). The resultant mixture was stirred at room temperature overnight, then washed with H2O first, the aqueous layer was extracted with DCM (2×50 mL). The combined organic layer was dried over Na2SO4. The crude product was purified on SiO2 gel column eluted with 30-40% EtOAc in hexanes to give 1-[3-({(2R)4-[4-fluoro-2-(trifluoromethyl)phenyl]-2-methylpiperazin-1-yl}sulfonyl)phenyl]ethanone as an off white solid (3.7 g, 90%). Step 3: To 1-[3-({(2R)4-[4-fluoro-2-(trifluoromethyl)phenyl]-2-methylpiperazin-1-yl}sulfonyl)phenyl]ethanone (3.7 g, 8.33 mmol) was added TMS-CF3 (50 mL, 25 mmol, 0.5 M in THF) at room temperature. This was cooled down to 0° C. in an ice bath, then TBAF (8.33 mL, 8.33 mmol, 1.0 M in THF) was added slowly. The resultant mixture was stirred at 0° C. for 30 min, then stirred at room temperature for 5 hours. The resultant mixture was diluted with saturated NaHCO3 (40 mL), washed with DCM (100 mL). This was separated, the organic layer washed with saturated brine, dried over Na2SO4. The crude product was purified on SiO2 gel column eluted with 30-50% EtOAc in Hexanes first, then purified again on SiO2 gel column eluted with 2.5% MeOH in DCM to give 1,1,1-trifluoro-2-[3-({(2R)4-[4-fluoro-2-(trifluoromethyl)phenyl]-2-methylpiperazin-1-yl}sulfonyl)phenyl]propan-2-ol as a white solid (2.76 g, 64%).

Workup

  1. washwashed with DCM (100 mL)
  2. customThis was separated
  3. washthe organic layer washed with saturated brine
  4. dry with materialdried over Na2SO4
  5. customThe crude product was purified on SiO2 gel column
  6. washeluted with 30-50% EtOAc in Hexanes first
  7. custompurified again on SiO2 gel column
  8. washeluted with 2.5% MeOH in DCM

Sources & evidence

ORD record
ord-dde0332dce4c43098a8fbc348dc948ee
Source dataset
uspto-grants-2009_12
Patent number
US07632838B2

Reaction notes

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