1-Isopropylpiperazine → 3-(4-Isopropylpiperazin-1-yl)benzaldehyde

HRID 1519449Notes

Reaction equation

HRID 1519449 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:8]2[O:13]CCCO2)[CH:5]=[CH:6][CH:7]=1.[CH:14]([N:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1)([CH3:16])[CH3:15].C(O[Na])(C)(C)C>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[CH:14]([N:17]1[CH2:22][CH2:21][N:20]([C:2]2[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=2)[CH:8]=[O:13])[CH2:19][CH2:18]1)([CH3:16])[CH3:15]

Participants

7

Reactant 3

HCID 780131-IsopropylpiperazineHCID 101058152-(3-Bromophenyl)-1,3-dioxaneHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 840175373-(4-Isopropylpiperazin-1-yl)benzaldehydeYield 87.4%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-(3-bromophenyl)-1,3-dioxane (2, 1.58 g, 6.5 mmol), 1-isopropylpiperazine (1.0 g, 7.8 mmol), rac-BINAP (60 mg, 0.096 mmol), and tert-BuONa (1.06 g, 11.1 mmol) in toluene (15 mL) was degassed under vacuum and flushed with nitrogen. Pd2(dba)3 (30 mg, 0.033 mmol) was added. The reaction mixture was degassed again and flushed with nitrogen and was heated at 100° C. under nitrogen for 16 h. The reaction mixture was poured into cold 1N HCl (30 mL) and stirred for 2 h. It was adjusted to pH 8 with 6N NaOH and extracted with EtOAc (3×50 mL). The combined organic layers were dried (MgSO4), filtered, concentrated, and purified by silica gel chromatography eluting with 0-100% EtOAc (containing 5% v/v Et3N) in hexanes to afford the title compound as a viscous yellow oil (1.32 g, 87%): 1H NMR (500 MHz, CDCl3) δ 9.96 (s, 1H), 7.44-7.37 (m, 2H), 7.34-7.30 (m, 1H), 7.21-7.16 (m, 1H), 3.28 (t, J=5.0 Hz, 4H), 2.73 (sept, J=6.5 Hz, 1H), 2.69 (t, J=5.0 Hz, 4H), 1.10 (d, J=6.5 Hz, 6H); ESI MS m/z 233 [M+H]+.

Workup

  1. customwas degassed under vacuum
  2. customflushed with nitrogen
  3. customThe reaction mixture was degassed again
  4. customflushed with nitrogen
  5. additionThe reaction mixture was poured into cold 1N HCl (30 mL)
  6. extractionextracted with EtOAc (3×50 mL)
  7. dry with materialThe combined organic layers were dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by silica gel chromatography
  11. washeluting with 0-100% EtOAc (
  12. additioncontaining 5% v/v Et3N) in hexanes

Sources & evidence

ORD record
ord-18a2b987a01b456fb075fe83c8f43194
Source dataset
uspto-grants-2015_07
Patent number
US09073878B2

Reaction notes

Loading…