Furan → HCID 21258205, compound

HRID 635213Notes

Reaction equation

HRID 635213 reaction equation
[O:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.C([Li])CCC.[Br:11][C:12]1[CH:17]=[C:16]([CH:18]([CH3:20])[CH3:19])[CH:15]=[CH:14][C:13]=1[N:21]([C:24]1[N:29]=[C:28]([N:30]2[CH2:35][CH2:34][C:33](=[O:36])[CH2:32][CH2:31]2)[CH:27]=[C:26]([CH3:37])[N:25]=1)[CH2:22][CH3:23].[Cl-].[NH4+]>O1CCCC1.CCCCCC>[Br:11][C:12]1[CH:17]=[C:16]([CH:18]([CH3:19])[CH3:20])[CH:15]=[CH:14][C:13]=1[N:21]([C:24]1[N:29]=[C:28]([N:30]2[CH2:35][CH2:34][C:33]([C:2]3[O:1][CH:5]=[CH:4][CH:3]=3)([OH:36])[CH2:32][CH2:31]2)[CH:27]=[C:26]([CH3:37])[N:25]=1)[CH2:22][CH3:23]

Participants

7

Reactant 4

HCID 8029FuranHCID 25517Ammonium ChlorideHCID 21258201HCID 21258201, compoundHCID 178418339Butyllithium

Product 1

HCID 21258205HCID 21258205, compoundYield 55.8%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-15 °C

Procedure

To a solution of 136 mg of furan in 1 ml of tetrahydrofuran was added dropwise 0.9 ml of a 1.63M n-hexane solution of n-butyl lithium under cooling at −15° C. over 10 minutes, followed by stirring at 5° C. for 20 minutes. To the reaction mixture was added dropwise a solution of 432 mg of 2-[N-(2-bromo-4-isopropylphenyl)-N-ethylamino]-6-methyl-4-(4-oxopiperidin-1-yl)pyrimidine in 2 ml of tetrahydrofuran over 10 minutes while cooling to −15° C., followed by stirring at −15° to 0° C. for 30 minutes. After stirring at room temperature for 1 hour, a saturated aqueous solution of ammonium chloride was added thereto dropwise under ice-cooling, and the mixture was extracted with ethyl acetate. The extract was washed successively with a saturated ammonium chloride aqueous solution, a saturated sodium hydrogencarbonate aqueous solution and a saturated sodium chloride aqueous solution, and dried over anhydrous sodium sulfate. The desiccant was removed by filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate=3/1) to give 279 mg of 2-[N-(2-bromo-4-isopropylphenyl)-N-ethylamino]-4-[4-(furan-2-yl)-4-hydroxypiperidin-1-yl]-6-methylpyrimidine.

Workup

  1. temperaturewhile cooling to −15° C.
  2. stirringby stirring at −15° to 0° C. for 30 minutes
  3. stirringAfter stirring at room temperature for 1 hour
  4. temperaturedropwise under ice-cooling
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe extract was washed successively with a saturated ammonium chloride aqueous solution
  7. dry with materiala saturated sodium hydrogencarbonate aqueous solution and a saturated sodium chloride aqueous solution, and dried over anhydrous sodium sulfate
  8. customThe desiccant was removed by filtration
  9. concentrationthe filtrate was concentrated under reduced pressure
  10. customthe residue was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate=3/1)

Sources & evidence

ORD record
ord-5ae1e71b6e604e8699b81a68965b9163
Source dataset
uspto-grants-2001_02
Patent number
US06187781B1

Reaction notes

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