Potassium Hydroxide → Tert-butyl 4-(6-((3-chlorobenzyl)oxy)pyrazin-2-yl)piperazine-1-carboxylate

HRID 2182130Notes

Reaction equation

HRID 2182130 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[N:18][CH:17]=[C:16](Cl)[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:21][C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=1)[CH2:25][OH:26].[OH-].[K+]>C1(C)C=CC=CC=1.C1OCCOCCOCCOCCOCCOC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[N:18][CH:17]=[C:16]([O:26][CH2:25][C:24]3[CH:27]=[CH:28][CH:29]=[C:22]([Cl:21])[CH:23]=3)[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 701173-Chlorobenzyl alcoholHCID 18186946Tert-butyl 4-(6-chloropyrazin-2-YL)piperazine-1-carboxylate

Product 1

HCID 69732798Tert-butyl 4-(6-((3-chlorobenzyl)oxy)pyrazin-2-yl)piperazine-1-carboxylateYield 93.9%

Reagents, catalysts & solvents 2

HCID 2855718-Crown-6CatalystHCID 1140TolueneSolvent

Procedure

A mixture of 6′-chloro-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid tert-butyl ester (I-1a) (300 mg, 1.0 mmol), 3-chlorobenzyl alcohol (0.142 mL, 1.2 mmol), KOH (191 mg, 3.4 mmol) and 18-crown-6 (10.6 mg, 0.04 mmol) in toluene (6 mL) was stirred at reflux for 5.5 h and concentrated in vacuo. The residue was partitioned between H2O (30 mL) and CH2Cl2 (30 mL). The aqueous phase was separated and extracted with CH2Cl2 (2×30 mL). The combined organic extracts were dried and concentrated in vacuo. The crude product was purified by preparative TLC (5% MeOH in CH2Cl2) to afford the title compound (I-1b) (380 mg).

Workup

  1. temperatureat reflux for 5.5 h
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between H2O (30 mL) and CH2Cl2 (30 mL)
  4. customThe aqueous phase was separated
  5. extractionextracted with CH2Cl2 (2×30 mL)
  6. customThe combined organic extracts were dried
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by preparative TLC (5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-90dea26b23da42a99810b7f060c9deb5
Source dataset
uspto-grants-2005_05
Patent number
US06894050B2

Reaction notes

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