Sodium t-butoxide → HCID 24906104, compound

HRID 1868135Notes

Reaction equation

HRID 1868135 reaction equation
Br[C:2]1[CH:3]=[C:4]([S:8]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=3[C:24]([F:27])([F:26])[F:25])[CH2:13][C@H:12]2[CH3:28])(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.C[C:30]([O-])([CH3:32])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:23][C:20]1[CH:21]=[CH:22][C:17]([N:14]2[CH2:15][CH2:16][N:11]([S:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([N:14]4[CH2:32][CH2:30][N:11]([CH3:16])[CH2:12][CH2:13]4)[CH:3]=3)(=[O:10])=[O:9])[C@H:12]([CH3:28])[CH2:13]2)=[C:18]([C:24]([F:27])([F:26])[F:25])[CH:19]=1

Participants

4

Reactant 2

HCID 23676156Sodium t-butoxideHCID 57418360HCID 57418360, compound

Product 1

HCID 24906104HCID 24906104, compoundYield 155.8%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
110 °C

Procedure

A mixture of (2R)-1-[(3-bromophenyl)sulfonyl]-4-[4-fluoro-2-(trifluoromethyl)phenyl]-2-methylpiperazine (8 g, 16.667 mmol), N-Me-piperazine (2.22 mL, 20 mmol), bis-t-Bu-biphenylphosphine (298.2 mg, 1.0 mmol), tBuONa (2.4 g, 25 mmol) and Pd2(dba)3 (305.2 mg, 0.333 mmol) was mixed and purged with N2. Anhydrous toluene (80 mL) was added and purged with N2 again. The resultant mixture was heated in an oil bath at 110° C. under N2 for 5 hours. After cooling, diluted with EtOAc (100 mL), filtered through a pad of Celite and washed with EtOAc (100 mL). The combined organic layer washed with aq. NaHCO3. The aqueous layer was back extracted with EtOAc (2×50 mL). The combined organic layer was dried over Na2SO4. The crude product was purified on SiO2 gel column eluted with 0-25% MeOH in EtOAc to give the desired product as a light yellow solid (6.5 g, 78%). HRMS: calcd for C23H28F4N4O2S+H+, 501.19418. found (ESI-FTMS, [M+H]1+), 501.1944.

Workup

  1. additionwas mixed
  2. custompurged with N2
  3. additionAnhydrous toluene (80 mL) was added
  4. custompurged with N2 again
  5. temperatureAfter cooling
  6. additiondiluted with EtOAc (100 mL)
  7. filtrationfiltered through a pad of Celite
  8. washwashed with EtOAc (100 mL)
  9. washThe combined organic layer washed with aq. NaHCO3
  10. extractionThe aqueous layer was back extracted with EtOAc (2×50 mL)
  11. dry with materialThe combined organic layer was dried over Na2SO4
  12. customThe crude product was purified on SiO2 gel column
  13. washeluted with 0-25% MeOH in EtOAc

Sources & evidence

ORD record
ord-8f8a054176dd4ae58fa4a27d3031cd5c
Source dataset
uspto-grants-2009_12
Patent number
US07632838B2

Reaction notes

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