Imidazole → HCID 86726616, compound

HRID 1506160Notes

Reaction equation

HRID 1506160 reaction equation
[OH:1][CH2:2][CH:3]1[CH2:8][CH2:7][CH:6]([C:9]([OH:11])=O)[CH2:5][CH2:4]1.Cl.[CH3:13][NH:14][O:15][CH3:16].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.N1C=CN=C1.[C:53]([Si:57](Cl)([CH3:59])[CH3:58])([CH3:56])([CH3:55])[CH3:54]>C(Cl)(Cl)Cl.O>[Si:57]([O:1][CH2:2][CH:3]1[CH2:4][CH2:5][CH:6]([C:9]([N:14]([O:15][CH3:16])[CH3:13])=[O:11])[CH2:7][CH2:8]1)([C:53]([CH3:56])([CH3:55])[CH3:54])([CH3:59])[CH3:58]

Participants

10

Reactant 7

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 202819Cyclohexanecarboxylic acid, 4-(hydroxymethyl)-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 86726616HCID 86726616, compoundYield 65%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6212ChloroformSolvent

Procedure

4-(Hydroxymethyl)cyclohexanecarboxic acid (25.0 g, 158 mmol) and N,O-dimethylhydroxylamine hydrochloride (23.1 g, 237 mmol) in chloroform (100 mL) were mixed with 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (36.4 g, 190 mmol), 1-hydroxybenzotriazole (5.00 g, 37.0 mmol) and N,N-diisopropylethylamine (41.3 mL, 237 mmol) and stirred at room temperature for 1 day. After addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was dissolved in N,N-dimethylformamide (100 mL) and mixed with imidazole (21.5 g, 316 mmol) and tert-butylchlorodimethylsilane (26.2 g, 174 mmol). The reaction mixture was stirred at room temperature for 1 day. After addition of water, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=5/1→3/1 (v/v)) to give the title compound as a colorless oil (32.4 g, yield 65%).

Workup

  1. extractionthe reaction mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated sodium chloride
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in N,N-dimethylformamide (100 mL)
  6. stirringThe reaction mixture was stirred at room temperature for 1 day
  7. extractionthe reaction mixture was extracted with ethyl acetate
  8. washThe organic layer was washed with saturated sodium chloride
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=5/1→3/1 (v/v))

Sources & evidence

ORD record
ord-8e385436ceff4d01b9b824978f85fa58
Source dataset
uspto-grants-2015_12
Patent number
US09216999B2

Reaction notes

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