1-Methylpiperazine → HCID 68561555, compound

HRID 1161881Notes

Reaction equation

HRID 1161881 reaction equation
[CH2:1]([O:3][C:4](=[O:17])[CH2:5][C:6]1[C:11]([C:12]([F:15])([F:14])[F:13])=[CH:10][CH:9]=[C:8](Cl)[N:7]=1)[CH3:2].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.CC(C)([O-])C.[Na+].[CH3:70][N:71]1[CH2:76][CH2:75][NH:74][CH2:73][CH2:72]1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:3][C:4](=[O:17])[CH2:5][C:6]1[C:11]([C:12]([F:15])([F:14])[F:13])=[CH:10][CH:9]=[C:8]([N:74]2[CH2:75][CH2:76][N:71]([CH3:70])[CH2:72][CH2:73]2)[N:7]=1)[CH3:2]

Participants

6

Reactant 4

HCID 531671-MethylpiperazineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 72217216HCID 72217216, compound

Product 1

HCID 68561555HCID 68561555, compound

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

(6-Chloro-3-trifluoromethyl-pyridin-2-yl)-acetic acid ethyl ester (700 mg, 2.62 mmol), palladium(II) acetate (47 mg, 0.21 mmol) and rac-2,2′-Bis-diphenylphosphanyl-[1,1′]binaphthalene (65 mg, 0.10 mmol) are added to sodium tert-butoxide, which has been dried for 15 minutes at 60° C. under high vacuum (277 mg, 2.88 mmol). This mixture is suspended in dioxane (9 ml, degassed three times under high vacuum and purged with argon), and N-methyl piperazine (288 mg, 2.88 mmol) is added. The flask containing this suspension is immersed in a pre-heated oil bath (85° C.). After 15 minutes at 85° C., TLC analysis indicates complete consumption of starting materials. The reaction mixture is cooled to RT and poured under stirring into a mixture of conc. aqueous NH4Cl (100 ml) and EtOAc (100 ml). The aqueous layer is extracted with EtOAc. The organic layer is then washed once with conc. aqueous NH4Cl, dried over Na2SO4 and concentrated. Purification by FCC (CH2Cl2/MeOH 100:0 to 98:2 to 97:3 to 96:4 to 95:5 to 8:2) yields the title compound. 1H NMR (CDCl3, 400 MHz) δ 1.30 (t, J=7.8 Hz, 3H), 2.35 (s, 3H), 2.50-2.57 (m, 4H), 3.32-3.39 (m, 4H), 3.76 (s, 2H), 4.20 (q, J=7.8 Hz, 2H), 6.90 (d, J=8.9 Hz, 1H), 7.79 (d, J=8.9 Hz, 1H); ES-MS: 332.5 [M+H]+.

Workup

  1. customhas been dried for 15 minutes at 60° C. under high vacuum (277 mg, 2.88 mmol)
  2. additionThe flask containing this suspension
  3. customis immersed in a pre-heated oil bath
  4. custom(85° C.)
  5. customconsumption of starting materials
  6. additionpoured
  7. extractionThe aqueous layer is extracted with EtOAc
  8. washThe organic layer is then washed once with conc. aqueous NH4Cl
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated
  11. customPurification by FCC (CH2Cl2/MeOH 100:0 to 98:2 to 97:3 to 96:4 to 95:5 to 8:2)

Sources & evidence

ORD record
ord-6391a209d40b47feb11c428116c210e7
Source dataset
uspto-grants-2010_10
Patent number
US07820672B2

Reaction notes

Loading…