Hexane → HCID 57801494, compound

HRID 2101496Notes

Reaction equation

HRID 2101496 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:21]=[C:22]([Cl:24])[CH:23]=1)[CH2:5][N:6]1[CH:10]=[CH:9][N:8]=[C:7]1[CH2:11][NH:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=1.[Li]CCCC.CCCCCC.[C:36]([O:40][C:41]([N:43]1[CH2:48][CH2:47][N:46]([CH2:49][CH2:50]Cl)[CH2:45][CH2:44]1)=[O:42])([CH3:39])([CH3:38])[CH3:37]>C1COCC1>[C:36]([O:40][C:41]([N:43]1[CH2:48][CH2:47][N:46]([CH2:49][CH2:50][N:12]([CH2:11][C:7]2[N:6]([CH2:5][C:4]3[CH:21]=[C:22]([Cl:24])[CH:23]=[C:2]([Cl:1])[CH:3]=3)[CH:10]=[CH:9][N:8]=2)[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)[CH2:45][CH2:44]1)=[O:42])([CH3:39])([CH3:38])[CH3:37]

Participants

6

Reactant 4

HCID 8058HexaneHCID 11951591HCID 11951591, compoundHCID 22106269tert-Butyl 4-(2-chloroethyl)piperazinecarboxylateHCID 178418339Butyllithium

Product 1

HCID 57801494HCID 57801494, compoundYield 44.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of [1-(3,5-dichloro-benzyl)-1H-imidazol-2-ylmethyl]-(3-fluoro-benzyl)-amine (146 mg, 0.4 mmol) in THF (1 mL) at −78° C. was added dropwise a solution of n-BuLi in hexane (0.19 mL, 0.44 mmol) and the mixture stirred at −78° C. for 30 min. A solution of 4-(2-Chloro-ethyl)-piperazine-1-carboxylic acid tert-butyl ester (116 mg, 0.46 mmol) in THF (1 mL) was then added dropwise and the mixture allowed to warm to ambient temperature before stirring for an additional 24 h. The reaction was quenched with water (10 mL) and extracted with CH2Cl2 (2×40 mL). The combined CH2Cl2 extracts were dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (silica gel, 20:1 CH2Cl2/MeOH) to provide 4-{2-[[1-(3,5-dichloro-benzyl)-1H-imidazol-2-ylmethyl]-(3-fluoro-benzyl)-amino]-ethyl}-piperazine-1-carboxylic acid tert-butyl ester (102 mg, 44%) as a colorless viscous oil: ESI MS m/z 576 [C29H36Cl2FN5O2+H]+.

Workup

  1. temperatureto warm to ambient temperature
  2. stirringbefore stirring for an additional 24 h
  3. customThe reaction was quenched with water (10 mL)
  4. extractionextracted with CH2Cl2 (2×40 mL)
  5. dry with materialThe combined CH2Cl2 extracts were dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (silica gel, 20:1 CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-388f4261eac94a31bd25573e849ae8f5
Source dataset
uspto-grants-2009_08
Patent number
US07572921B2

Reaction notes

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