3-Methoxyphenethyl alcohol → 2-[2-(3-Methoxyphenyl)ethoxy]-6-(4-piperidinyloxy)pyrazine

HRID 1296648Notes

Reaction equation

HRID 1296648 reaction equation
Cl[C:2]1[CH:7]=[N:6][CH:5]=[C:4]([O:8][CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[N:3]=1.[CH3:15][O:16][C:17]1[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=1)[CH2:20][CH2:21][OH:22]>CN(C=O)C>[CH3:15][O:16][C:17]1[CH:18]=[C:19]([CH2:20][CH2:21][O:22][C:2]2[CH:7]=[N:6][CH:5]=[C:4]([O:8][CH:9]3[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]3)[N:3]=2)[CH:23]=[CH:24][CH:25]=1

Participants

4

Reactant 2

HCID 787243-Methoxyphenethyl alcoholHCID 181869152-Chloro-6-(4-piperidinyloxy)pyrazine

Product 1

HCID 181868082-[2-(3-Methoxyphenyl)ethoxy]-6-(4-piperidinyloxy)pyrazine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of the product obtained in Step 2 above (0.043 g, 0.20 mmol) in DMF (1.1 mL) was added to a mixture of 3-methoxyphenethyl alcohol (0.061 g, 0.40 mmol) and K-t-BuO (1.0 M in tert-butanol; 0.4 mL, 0.40 mmol) in DMF (0.8 mL). The reaction mixture was vortexed for 16 h at 50° C. under nitrogen, quenched with water (0.1 mL) and concentrated in vacuo. The residue was partitioned between water (2 mL) and 4 ethyl acetate (4 mL) and poured through a hydromatrix column, which was eluted with ethyl acetate/Et3N (95:5). Solvents were evaporated off and the residue was dissolved in methanol/water (50 mL) and loaded onto a conditioned weak cation exchange SPE column (1 g, Amberlyst CG-50 I). The column was washed with water (10 mL) and methanol (10 mL). The compound was eluted with aqueous 2.0 M NH3 in methanol (20 m) and concentrated in vacuo. The residue was analysed for identity and purity by LC-UV/MS. Yield: 8 mg (12%). HRMS m/z calcd for C18H23N3O3 (M)+ 329.1739, found 329.1743.

Workup

  1. customquenched with water (0.1 mL)
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between water (2 mL) and 4 ethyl acetate (4 mL)
  4. additionpoured through a hydromatrix column, which
  5. washwas eluted with ethyl acetate/Et3N (95:5)
  6. customSolvents were evaporated off
  7. dissolutionthe residue was dissolved in methanol/water (50 mL)
  8. washThe column was washed with water (10 mL) and methanol (10 mL)
  9. washThe compound was eluted with aqueous 2.0 M NH3 in methanol (20 m)
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6978057f4bac4351896e587e173fb43b
Source dataset
uspto-grants-2007_07
Patent number
US07247633B2

Reaction notes

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