Sodium Hydroxide → 2-[1-[2-[4-(p-Toluidino)piperidin-1-yl]ethyl]cyclobutyl]ethanol

HRID 2223925Notes

Reaction equation

HRID 2223925 reaction equation
FC(F)(F)C(O)=O.[C:8]1([CH3:21])[CH:13]=[CH:12][C:11]([NH:14][CH:15]2[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)=[CH:10][CH:9]=1.[CH2:22]1[C:25]2([CH2:30][CH2:29][O:28][CH:27](O)[CH2:26]2)[CH2:24][CH2:23]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>O1CCCC1.C(N(CC)CC)C>[C:8]1([CH3:21])[CH:9]=[CH:10][C:11]([NH:14][CH:15]2[CH2:20][CH2:19][N:18]([CH2:29][CH2:30][C:25]3([CH2:26][CH2:27][OH:28])[CH2:22][CH2:23][CH2:24]3)[CH2:17][CH2:16]2)=[CH:12][CH:13]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 23020925HCID 23020925, compoundHCID 59714887HCID 59714887, compound

Product 1

HCID 597149572-[1-[2-[4-(p-Toluidino)piperidin-1-yl]ethyl]cyclobutyl]ethanolYield 75.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Procedure

To a suspension of 4-(p-toluidino)piperidine trifluoroacetate (418 mg) (synthesized in Preparation Example 4-5) in tetrahydrofuran (3 mL) was added triethylamine (0.28 mL). The solution was stirred at room temperature for 5 minutes. Then, 7-oxaspiro[3.5]nonan-6-ol (104 mg) (synthesized in Example 65) in tetrahydrofuran (3 mL) was added to the solution and it was stirred at room temperature for additional 10 minutes. The reaction solution was ice-cooled and sodium triacetoxyborohydride (424 mg) was added thereto. The solution was then 4lowed for its temperature to rise to room temperature. The solution was stirred for additional 4.5 hours. A 3N aqueous sodium hydroxide solution (5 mL) was added to the reaction solution and it was extracted with tert-butyl methyl ether. The resulting residue was purified by chromatography [NH silica gel, hexane-ethyl acetate (7:3)] to give the title compound (175 mg).

Workup

  1. stirringwas stirred at room temperature for additional 10 minutes
  2. temperaturecooled
  3. customto rise to room temperature
  4. stirringThe solution was stirred for additional 4.5 hours
  5. extractionwas extracted with tert-butyl methyl ether
  6. customThe resulting residue was purified by chromatography [NH silica gel, hexane-ethyl acetate (7:3)]

Sources & evidence

ORD record
ord-80891a1ab86d4120bed43ed7d5669fe2
Source dataset
uspto-grants-2008_05
Patent number
US07375115B2

Reaction notes

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