Hexane → Tert-butyl 4-({1-[2-(4-cyanophenyl)ethyl]-4-hydroxypiperidin-4-ylmethyl}methylamino)benzoate

HRID 967780Notes

Reaction equation

HRID 967780 reaction equation
CCCCCC.C([Li])CCC.[CH3:12][NH:13][C:14]1[CH:26]=[CH:25][C:17]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:16][CH:15]=1.[C:27]([C:29]1[CH:34]=[CH:33][C:32]([CH2:35][CH2:36][N:37]2[CH2:44][CH2:43][C:40]3([CH2:42][O:41]3)[CH2:39][CH2:38]2)=[CH:31][CH:30]=1)#[N:28]>O.O1CCCC1>[C:27]([C:29]1[CH:34]=[CH:33][C:32]([CH2:35][CH2:36][N:37]2[CH2:44][CH2:43][C:40]([CH2:42][N:13]([CH3:12])[C:14]3[CH:15]=[CH:16][C:17]([C:18]([O:20][C:21]([CH3:22])([CH3:23])[CH3:24])=[O:19])=[CH:25][CH:26]=3)([OH:41])[CH2:39][CH2:38]2)=[CH:31][CH:30]=1)#[N:28]

Participants

7

Reactant 4

HCID 8058HexaneHCID 22291264tert-Butyl 4-(methylamino)benzoateHCID 858197211-[2-(4-Cyanophenyl)ethyl]piperidin-4-spiro-2'-oxiraneHCID 178418339Butyllithium

Product 1

HCID 22930217Tert-butyl 4-({1-[2-(4-cyanophenyl)ethyl]-4-hydroxypiperidin-4-ylmethyl}methylamino)benzoateYield 49.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A hexane solution of n-butyllithium (1.57M; 2.68 mL) was added dropwise to an anhydrous tetrahydrofuran solution (4.22 mL) of the compound (874 mg) obtained in Step 1 at the internal temperature of below 5° C. and the mixture was stirred under cooling with ice-water for one hour. To the mixture was added dropwise an anhydrous tetrahydrofuran solution (4.22 mL) of the compound (1.02 g) obtained in Step 3 of Example 1 at the internal temperature of below 5° C. over thirty minutes, stirred at the same temperature for one hour and further at room temperature for fifty two hours. To the solution added water (40 mL) under cooling with ice-water and the residue was extracted with ethyl acetate. After the organic layer was washed with brine and dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (Chromatorex NH™)(eluent; hexane:ethyl acetate=7:3 to 1:1) to obtain the titled compound (940 mg) as powder.

Workup

  1. stirringstirred at the same temperature for one hour and further at room temperature for fifty two hours
  2. extractionthe residue was extracted with ethyl acetate
  3. washAfter the organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe solvent was removed under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (Chromatorex NH™)(eluent; hexane:ethyl acetate=7:3 to 1:1)

Sources & evidence

ORD record
ord-345b9e7aaf85473fb9d57b2dfe08d1b0
Source dataset
uspto-grants-2005_10
Patent number
US06956046B2

Reaction notes

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