Ammonium Chloride → HCID 59171005, compound

HRID 2247622Notes

Reaction equation

HRID 2247622 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:11][N:12]1[CH:17]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:16][CH2:15][CH2:14][C:13]1=[O:24].[CH3:25][O:26][C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][C:34]=1[N:35]1[CH:39]=[C:38]([CH3:40])[N:37]=[CH:36]1)[CH:30]=O.[Cl-].[NH4+]>C1COCC1.C(OCC)(=O)C>[CH3:25][O:26][C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][C:34]=1[N:35]1[CH:39]=[C:38]([CH3:40])[N:37]=[CH:36]1)/[CH:30]=[C:14]1/[C:13](=[O:24])[N:12]([CH3:11])[CH:17]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:16][CH2:15]/1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 272824453-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehydeHCID 45024355HCID 45024355, compound

Product 1

HCID 59171005HCID 59171005, compoundYield 1.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Lithium bis(trimethylsilyl)amide (1.0 M solution in THF, 1.59 mL) was added dropwise to a solution of 1-methyl-6-phenylpiperidin-2-one (200 mg) synthesized in accordance with a technique described in a document (see N. P. Baens et al., “Tetrahedron”, 1993, vol. 49, pp. 3193-3202, for example) in THF (5 mL) at −78° C., and the reaction solution was stirred at room temperature for 30 minutes. This solution was added dropwise to a solution of 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehyde (248 mg) and a boron trifluoride-dimethyl ether complex (134 μL) in THF at −78° C., and the reaction solution was stirred overnight while heating to room temperature. A saturated aqueous solution of ammonium chloride and ethyl acetate were added to the reaction solution and the organic layer was partitioned. The organic layer was washed with brine, and then dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system) to collect the part in which an aldol derivative eluted. The elution part was concentrated under reduced pressure. Methanesulfonyl chloride (33.9 mg), triethylamine (206 μL) and methylene chloride (25 mL) were added to the residue, and the reaction solution was stirred at room temperature for 3 days. Water and ethyl acetate were added to the reaction solution and the organic layer was partitioned. The organic layer was washed with brine, and then dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by LC-MS to obtain 4.54 mg of the title compound. Properties data of the compound are as follows.

Workup

  1. customsynthesized in accordance with a technique
  2. customat −78° C.
  3. customwas stirred at room temperature for 30 minutes
  4. customthe organic layer was partitioned
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system)
  9. customto collect the part in which an aldol derivative eluted
  10. concentrationThe elution part was concentrated under reduced pressure
  11. additionMethanesulfonyl chloride (33.9 mg), triethylamine (206 μL) and methylene chloride (25 mL) were added to the residue
  12. additionWater and ethyl acetate were added to the reaction solution
  13. customthe organic layer was partitioned
  14. washThe organic layer was washed with brine
  15. dry with materialdried over anhydrous magnesium sulfate
  16. concentrationconcentrated under reduced pressure
  17. customThe residue was purified by LC-MS

Sources & evidence

ORD record
ord-fb75dcf5798b41c78d93ac751f9b8042
Source dataset
uspto-grants-2010_03
Patent number
US07687640B2

Reaction notes

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