Piperidine → HCID 67266161, compound

HRID 1685323Notes

Reaction equation

HRID 1685323 reaction equation
O=[CH:2][C:3]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:4][NH:5][C:6](=[O:12])[O:7][C:8]([CH3:11])([CH3:10])[CH3:9].[NH:25]1[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1.[BH4-].[Na+]>C(O)C.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[C:19]1([C:3]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)([CH2:2][N:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)[CH2:4][NH:5][C:6](=[O:12])[O:7][C:8]([CH3:9])([CH3:11])[CH3:10])[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

6

Reactant 3

HCID 8082PiperidineHCID 4311764Sodium borohydrideHCID 59200439HCID 59200439, compound

Product 1

HCID 67266161HCID 67266161, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 702EthanolSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of tert-butyl 3-oxo-2,2-diphenylpropylcarbamate (0.60 g, 1.844 mmol) and piperidine (0.314 g, 3.688 mmol) in ethanol (10 mL) was treated with titanium isopropoxide (1.62 mL, 5.53 mmol) and this was stirred at 65° C. overnight. The reaction was then cooled down to 23° C. and sodium borohydride (0.279 g, 7.38 mmol) was added. The reaction was stirred for 2 more hours, then quenched with 10% ammonium hydroxide (10 mL), diluted with ethyl acetate and stirred for 30 minutes. The solid was removed by filtration and the filtrate was acidified with 1N HCl and washed with ethyl acetate. The filtrate was then basified with sat. aq. sodium bicarbonate and extracted with ethyl acetate (3×). The combined organic extracts were dried over anhydrous magnesium sulfate, filtered and concentrated to give the crude title material (0.28 g) as a colorless film. This was purified by silica gel chromatography (Biotage, ethyl acetate/hexane 20% to 50%) to give tert-butyl 2,2-diphenyl-3-(piperidin-1-yl)propylcarbamate (0.13 g, 18%) as an oil. 1H NMR (400 MHz, CDCl3) δ ppm: 1.28-1.46 (6H, m), 1.41 (9H, s), 2.04-2.11 (4H, m), 3.06 (2H, br s), 3.98 (2H, d, J=5.56 Hz), 7.19-7.30 (10H, m). HPLC ret. time (Condition B): 2.633 min. LC/MS (M+H)+: 395.

Workup

  1. temperatureThe reaction was then cooled down to 23° C.
  2. stirringThe reaction was stirred for 2 more hours
  3. customquenched with 10% ammonium hydroxide (10 mL)
  4. additiondiluted with ethyl acetate
  5. stirringstirred for 30 minutes
  6. customThe solid was removed by filtration
  7. washwashed with ethyl acetate
  8. extractionextracted with ethyl acetate (3×)
  9. dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto give the crude title material (0.28 g) as a colorless film
  13. customThis was purified by silica gel chromatography (Biotage, ethyl acetate/hexane 20% to 50%)

Sources & evidence

ORD record
ord-58dc0418098542d1aa9318cdb0a83e98
Source dataset
uspto-grants-2012_04
Patent number
US08148400B2

Reaction notes

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