Cesium carbonate → 1-(3-(1,3-Dioxolan-2-yl)-5-(trifluoromethoxy)phenyl)-4-isopropylpiperazine

HRID 922383Notes

Reaction equation

HRID 922383 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:13]2[O:17][CH2:16][CH2:15][O:14]2)[CH:5]=[C:6]([O:8][C:9]([F:12])([F:11])[F:10])[CH:7]=1.[CH:18]([N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1)([CH3:20])[CH3:19].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>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].C1(C)C=CC=CC=1>[O:14]1[CH2:15][CH2:16][O:17][CH:13]1[C:4]1[CH:3]=[C:2]([N:24]2[CH2:25][CH2:26][N:21]([CH:18]([CH3:20])[CH3:19])[CH2:22][CH2:23]2)[CH:7]=[C:6]([O:8][C:9]([F:12])([F:11])[F:10])[CH:5]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 780131-IsopropylpiperazineHCID 634876Binap, (A+-)-HCID 867193482-[3-Bromo-5-(trifluoromethoxy)phenyl]-1,3-dioxolane

Product 1

HCID 867193491-(3-(1,3-Dioxolan-2-yl)-5-(trifluoromethoxy)phenyl)-4-isopropylpiperazineYield 70%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Tris(dibenzylideneacetone)dipalladium(0) (363 mg, 0.396 mmol) was added to a suspension of 2-(3-bromo-5-(trifluoromethoxy)phenyl)-1,3-dioxolane (21, 1.24 g, 3.96 mmol), isopropylpiperazine (610 mg, 4.75 mmol), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (rac-BINAP, 345 mg, 0.554 mmol), cesium carbonate (2.58 g, 7.92 mmol) and anhydrous toluene (50 mL). The mixture was placed under nitrogen and heated to 100° C. for 17 h. The solvent was removed in vacuo and methanol (30 mL) and silica gel (30 g) were added. After removing the methanol the adsorbed crude product was purified by silica gel chromatography eluting with 0-60% EtOAc in hexanes to afford the title compound (996 mg, 70%) as an orange oil: 1H NMR (500 MHz, CDCl3) δ 6.93 (s, 1H), 6.78 (s, 1H), 6.68 (s, 1H), 5.77 (s, 1H), 4.17-3.99 (m, 4H), 3.26-3.22 (m, 4H), 2.72 (sept, 1H), 2.68-2.62 (m, 4H), 1.08 (d, J=6.5 Hz, 6H).

Workup

  1. customThe solvent was removed in vacuo and methanol (30 mL) and silica gel (30 g)
  2. additionwere added
  3. customAfter removing the methanol the adsorbed crude product
  4. customwas purified by silica gel chromatography
  5. washeluting with 0-60% EtOAc in hexanes

Sources & evidence

ORD record
ord-eecd8dca9bd24397941c1c032c4b3412
Source dataset
uspto-grants-2016_03
Patent number
US09278940B2

Reaction notes

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