Water → HCID 10759909, compound

HRID 1459720Notes

Reaction equation

HRID 1459720 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:15]1([CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][NH:22]2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C([BH3-])#N.[Na+].O>CO.C(OCC)(=O)C.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:22]2[CH2:23][CH2:24][CH2:25][CH2:26][CH:21]2[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 962WaterHCID 1030202-PhenylpiperidineHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5003444Sodium cyanoborohydride

Product 1

HCID 10759909HCID 10759909, compoundYield 3%

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

N-tert-Butyloxycarbonyl-4-piperidone (5 g), 2-phenylpiperidine (4.03 g) and titanium isopropoxide (8.9 ml) were stirred at room temperature under a nitrogen atmosphere for 3 h. The resulting orange solution was diluted with methanol (40 ml), treated with sodium cyanoborohydride (1.6 g), and stirred for 20 h. Water (50 ml) was added to give a granular precipitate which was removed by filtration through celite. The filtrate was partitioned between water-ethyl acetate, the organic phase separated, dried (MgSO4) and concentrated. The residue was dissolved in ethyl acetate and washed with a saturated aqueous solution of citric acid. The aqueous phase was basified to pH10 using 4N sodium hydroxide, and extracted into ethyl acetate. The organic phase was dried (MgSO4) and concentrated. The residue was chromatographed using ethyl acetate-petroleum ether (20:80 to 50:50) to afford a partially purified mixture, which was dissolved in ethyl acetate. The organic phase was washed with a saturated aqueous solution of citric acid. The aqueous phase was separated, basified to pH10 using 4N sodium hydroxide and extracted with ethyl acetate. The organic phase was dried (MgSO4) and concentrated to give the product in 3% yield. δH (250 MHz, CDCl3) 1.16-1.79 (19H, m), 2.21-2.29 (2H, m), 2.41-2.50 (2H, m), 2.90-3.04 (1H, m), 3.36-3.44 (1H, m), 3.92-4.10 (2H, m), 7.16-7.40 (5H, m).

Workup

  1. customto give a granular precipitate which
  2. customwas removed by filtration through celite
  3. customThe filtrate was partitioned between water-ethyl acetate
  4. customthe organic phase separated
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in ethyl acetate
  8. washwashed with a saturated aqueous solution of citric acid
  9. extractionextracted into ethyl acetate
  10. dry with materialThe organic phase was dried (MgSO4)
  11. concentrationconcentrated
  12. customThe residue was chromatographed
  13. customto afford a partially purified mixture, which
  14. washThe organic phase was washed with a saturated aqueous solution of citric acid
  15. customThe aqueous phase was separated
  16. extractionextracted with ethyl acetate
  17. dry with materialThe organic phase was dried (MgSO4)
  18. concentrationconcentrated
  19. customto give the product in 3% yield

Sources & evidence

ORD record
ord-dbdcb3c791cf4750afc2d9b17f38c4cc
Source dataset
uspto-grants-1998_12
Patent number
US05854268

Reaction notes

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