1-Methylimidazole → HCID 69411984, compound

HRID 1592759Notes

Reaction equation

HRID 1592759 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[CH:3]1.[Li]CCCC.[C:12]([N:19]1[CH2:24][CH2:23][N:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[CH:31]=[O:32])[CH2:21][CH2:20]1)([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].[NH4+].[Cl-]>C1COCC1.CCCCCC.[Cl-].[Na+].O>[C:12]([N:19]1[CH2:20][CH2:21][N:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[CH:31]([OH:32])[C:3]2[N:2]([CH3:1])[CH:6]=[CH:5][N:4]=2)[CH2:23][CH2:24]1)([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13]

Participants

8

Reactant 4

HCID 13901-MethylimidazoleHCID 25517Ammonium ChlorideHCID 64909901-Boc-4-(2-formylphenyl)piperazineHCID 178418339Butyllithium

Product 1

HCID 69411984HCID 69411984, compoundYield 159%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1-methyl imidazole (350 uL, 4.4 mmol) in 15 mL of THF at −78° C. was added n-BuLi (1.5 mL of a 1.6 M solution in hexane, 2.4 mmol). After stirring for about 30 minutes, the solution was warmed to about 0° C. and then stirred for about 15 minutes. The mixture was then cooled to about −78° C. A solution of N-Boc-4-(2-formylphenyl)-piperazine (580 mg, 1.0 mmol) in 5 mL of THF was added via cannula The solution was allowed to warm slowly to r.t. overnight. After addition of saturated aqueous NH4Cl and brine, the solution was extracted with EtOAc (2×). The combined organic solutions were dried (Na2SO4), filtered and concentrated. Purification by silica gel chromatography (35 g SiO2, 0 to 10% 0.2 M NH3 in MeOH/CH2Cl2 over 30 min at 35 mL/min) afforded about 592 mg (1.59 mmol, 79%) of the alcohol as a colorless oil. LRMS (ESI+): 373.2 (M+1)

Workup

  1. stirringstirred for about 15 minutes
  2. temperatureThe mixture was then cooled to about −78° C
  3. temperatureto warm slowly to r.t. overnight
  4. extractionthe solution was extracted with EtOAc (2×)
  5. dry with materialThe combined organic solutions were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by silica gel chromatography (35 g SiO2, 0 to 10% 0.2 M NH3 in MeOH/CH2Cl2 over 30 min at 35 mL/min)

Sources & evidence

ORD record
ord-309e685c9955497d86c92a5d4d13b8c9
Source dataset
uspto-grants-2007_11
Patent number
US07291619B2

Reaction notes

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