1-t-Butoxycarbonyl-4-{1-(4-fluorophenyl)-2-[4-(naphthalen-1-yl-butyl)piperazin-1-yl]-2-oxoethyl}-4-hydroxypiperidine → 4-{1-(4-Fluorophenyl)-2-[4-(naphthalen-1-yl-butyl)piperazin-1-yl]-2-oxoethyl}-1-methylpiperidin-4-ol

HRID 497342Notes

Reaction equation

HRID 497342 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH:15]([C:38]2[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=2)[C:16]([N:18]2[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][CH2:26][CH2:27][C:28]3[C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[CH:31]=[CH:30][CH:29]=3)[CH2:20][CH2:19]2)=[O:17])([OH:14])[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.O1CCOCC1>CO>[F:44][C:41]1[CH:42]=[CH:43][C:38]([CH:15]([C:11]2([OH:14])[CH2:10][CH2:9][N:8]([CH3:6])[CH2:13][CH2:12]2)[C:16]([N:18]2[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][CH2:26][CH2:27][C:28]3[C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[CH:31]=[CH:30][CH:29]=3)[CH2:20][CH2:19]2)=[O:17])=[CH:39][CH:40]=1

Participants

4

Reactant 2

HCID 178506631-t-Butoxycarbonyl-4-{1-(4-fluorophenyl)-2-[4-(naphthalen-1-yl-butyl)piperazin-1-yl]-2-oxoethyl}-4-hydroxypiperidineHCID 204431481,4-Dioxane hydrochloride

Product 1

HCID 178506574-{1-(4-Fluorophenyl)-2-[4-(naphthalen-1-yl-butyl)piperazin-1-yl]-2-oxoethyl}-1-methylpiperidin-4-olYield 49.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1.04 g of 1-t-Butoxycarbonyl-4-{1-(4-fluorophenyl)-2-[4-(naphthalen-1-yl-butyl)piperazin-1-yl]-2-oxoethyl}-4-hydroxypiperidine was dissolved in 10 ml of methanol, and 20 ml of 4M hydrogen chloride/1,4-dioxane solution was added, followed by stirring at room temperature for 2 hours. The reaction solution was concentrated under reduced pressure, ethyl acetate was added to the residue, and the mixture was washed with 1M aqueous sodium hydroxide solution and a saturated aqueous sodium solution. The organic layer was dried over anhydrous sodium sulfate. After removal of the drying agent by filtration, the filtrate was concentrated under reduced pressure. The residue was dissolved in 9 ml of acetonitrile, and 640 μl of 37% formalin, 190 μl of acetic acid and 160 mg of sodium cyanoborohydride were added, followed by stirring at room temperature for an hour. The reaction solution was diluted with ethyl acetate and washed with a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate. After removal of the drying agent by filtration, the filtrate was concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (Chromatorex NH, hexane:ethyl acetate=2:1) to give 0.44 g of 4-{1-(4-fluorophenyl)-2-[4-(naphthalen-1-yl-butyl)piperazin-1-yl]-2-oxoethyl}-1-methylpiperidin-4-ol as an oil.

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure, ethyl acetate
  2. additionwas added to the residue
  3. washthe mixture was washed with 1M aqueous sodium hydroxide solution
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. customAfter removal of the drying agent
  6. filtrationby filtration
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. dissolutionThe residue was dissolved in 9 ml of acetonitrile
  9. addition640 μl of 37% formalin, 190 μl of acetic acid and 160 mg of sodium cyanoborohydride were added
  10. stirringby stirring at room temperature for an hour
  11. additionThe reaction solution was diluted with ethyl acetate
  12. washwashed with a saturated aqueous sodium bicarbonate solution
  13. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  14. customAfter removal of the drying agent
  15. filtrationby filtration
  16. concentrationthe filtrate was concentrated under reduced pressure
  17. customThe residue was purified by a silica gel column chromatography (Chromatorex NH, hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-ed96e125308c4ff3ae3f480a52836016
Source dataset
uspto-grants-2005_09
Patent number
US06949552B2

Reaction notes

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