1,2-Dimethoxyethane → HCID 23142336, compound

HRID 32276Notes

Reaction equation

HRID 32276 reaction equation
[CH3:1][C:2]1([CH3:27])[CH2:7][C:6]([CH3:9])([CH3:8])[CH2:5][CH:4]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[N:16]2[CH2:21][CH2:20][N:19]([CH2:22][C:23](=O)[CH2:24][CH3:25])[CH2:18][CH2:17]2)[CH2:3]1.COCCOC.C1(C)C=CC(S([CH2:43][N+:44]#[C-])(=O)=O)=CC=1.CC(C)([O-])C.[K+].[Cl-:53].[Na+].O>C(OCC)(=O)C.C(O)(C)(C)C>[ClH:53].[CH3:1][C:2]1([CH3:27])[CH2:7][C:6]([CH3:9])([CH3:8])[CH2:5][CH:4]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[N:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH:23]([CH2:24][CH3:25])[C:43]#[N:44])[CH2:18][CH2:17]2)[CH2:3]1

Participants

8

Reactant 5

HCID 80711,2-DimethoxyethaneHCID 161915Tosylmethyl isocyanideHCID 11187849HCID 11187849, compoundHCID 23665647Potassium tert-butoxideHCID 57417360Sodium chloride; water

Product 1

HCID 23142336HCID 23142336, compound

Reagents, catalysts & solvents 2

HCID 6386tert-ButanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 1-{4-[2-(3,3,5,5-tetramethylcyclohexyl)phenyl]piperazin-1-yl}butan-2-one (80 mg, 0.21 mmol) produced as an intermediate in Example 25, 1,2-dimethoxyethane (2.5 mL) and t-butanol (0.1 mL) were added p-toluenesulfonylmethyl isocyanide (TosMIC) (46.4 mg, 0.238 mmol) and potassium t-butoxide (34 mg, 0.302 mmol) at an external temperature of 0° C., followed by stirring for 90 minutes under the same conditions. The external temperature was then raised to room temperature and stirring was continued for 30 minutes. Brine was added to the reaction mixture, extraction was performed with ethyl acetate, and the obtained organic layer was dried over anhydrous sodium sulfate. After removing the desiccant by filtration, the filtrate was concentrated under reduced pressure to give a residue, which was then purified by NH silica gel column chromatography (ethyl acetate/heptane) to give 66 mg of the free form of the title compound as a colorless oil. This compound (66 mg, 0.173 mmol) was dissolved in dichloromethane-ethyl acetate, and then a 4N solution of hydrogen chloride in ethyl acetate (0.046 mL, 0.18 mmol) was added. The mixed solution was concentrated under reduced pressure, and the resulting solid residue was washed with a diethyl ether-heptane mixed solvent and then dried under reduced pressure to give 65 mg of the title compound as a colorless solid.

Workup

  1. stirringstirring
  2. waitwas continued for 30 minutes
  3. dry with materialthe obtained organic layer was dried over anhydrous sodium sulfate
  4. customAfter removing the
  5. filtrationdesiccant by filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customto give a residue, which
  8. customwas then purified by NH silica gel column chromatography (ethyl acetate/heptane)

Sources & evidence

ORD record
ord-5ab95d257849450d902929fdbc3de064
Source dataset
uspto-grants-2008_09
Patent number
US07425554B2

Reaction notes

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