Sodium hydride → HCID 22036242, compound

HRID 1789769Notes

Reaction equation

[OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=1)[O:5][CH2:6][CH2:7][OH:8].[H-].[Na+].Cl[C:15]1[C:20]([N:21]2[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]2)=[N:19][CH:18]=[CH:17][N:16]=1>CN(C=O)C>[OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=1)[O:5][CH2:6][CH2:7][O:8][C:15]1[C:20]([N:21]2[CH2:22][CH2:23][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:25][CH2:26]2)=[N:19][CH:18]=[CH:17][N:16]=1

Participants

Conditions

Temperature: 65 °C

Procedure

To a stirred solution of 2-(3-hydroxyphenoxy)ethanol (7.71 g, 0.05 mol) in dry DMF to (100 mL) at ˜0° C. (ice bath) was added NaH (3.90 g, 0.163 mol) in portions under N2. When the H2-evolution had ceased, a solution of 2-chloro-3-(4-tert-butoxycarbonyl-1-piperazinyl)pyrazine (0.05 mol, 14.9 g; from Example 52, Step 1) in dry DMF (70 mL) was added in one portion. The mixture was stirred at 65° C. for 1.75 h. After cooling, the reaction was quenched by addition of H2O in DMF. The mixture was filtered and concentrated, in vacuo. The residue was dissolved in EtOAc, washed with 1 M KHSO4 and water, dried (Na2SO4+Norit), and concentrated in vacuo to give the title compound as a beige sticky oil. Yield 94%. This product was used directly in the next step without further purification.

Workup

temperatureAfter cooling
customthe reaction was quenched by addition of H2O in DMF
filtrationThe mixture was filtered
concentrationconcentrated, in vacuo
dissolutionThe residue was dissolved in EtOAc
washwashed with 1 M KHSO4 and water
dry with materialdried (Na2SO4+Norit)
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-cc362952def14ec9ad18caceddb44035
Source dataset: uspto-grants-2006_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07071180B2

Reaction notes

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