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

HRID 922396Notes

Reaction equation

HRID 922396 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(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

6

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 2

HCID 634876Binap, (A+-)-CatalystHCID 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. additionPd2(dba)3 (30 mg, 0.033. mmol) was added
  4. customThe reaction mixture was degassed again
  5. customflushed with nitrogen
  6. additionThe reaction mixture was poured into cold 1N HCl (30 mL)
  7. extractionextracted with EtOAc (3×50 mL)
  8. dry with materialThe combined organic layers were dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. custompurified by silica gel chromatography
  12. washeluting with 0-100% EtOAc (
  13. additioncontaining 5% v/v Et3N) in hexanes

Sources & evidence

ORD record
ord-77d2d82a3b094e058024114599dc4902
Source dataset
uspto-grants-2016_03
Patent number
US09278940B2

Reaction notes

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