tert-Butyl 4-oxopiperidine-1-carboxylate → HCID 86702079, compound

HRID 873593Notes

Reaction equation

HRID 873593 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]([Si](C)(C)C)[Si](C)(C)C)=[CH:4][CH:3]=1.[Li]CCCC.[O:22]=[C:23]1[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]1>O1CCCC1>[NH2:8][C:5]1[CH:6]=[CH:7][C:2]([C:23]2([OH:22])[CH2:24][CH2:25][N:26]([C:29]([O:31][C:32]([CH3:34])([CH3:33])[CH3:35])=[O:30])[CH2:27][CH2:28]2)=[CH:3][CH:4]=1

Participants

5

Reactant 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 40926204-Bromo-N,N-bis(trimethylsilyl)anilineHCID 178418339Butyllithium

Product 1

HCID 86702079HCID 86702079, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

N-(4-Bromophenyl)-1,1,1-trimethyl-N-(trimethylsilyl)silanamine (7 g, 22.12 mmol) in tetrahydrofuran (100 mL) was treated with a solution of n-BuLi (1M, 22 mL) at −78° C. The reaction mixture was stirred an additional hour at −78° C. and then treated with a solution of tert-butyl 4-oxopiperidine-1-carboxylate (3.97 g, 19.91 mmol) in tetrahydrofuran (20 mL). The reaction mixture was stirred at −78° C. for 30 minutes and then warmed to room temperature. The reaction was quenched by addition of saturated ammonium chloride solution (100 mL) and then was extracted with ethyl acetate. The combined organics were washed with water, brine, dried with magnesium sulfate, filtered and concentrated. The crude tert-butyl 4-(4-(bis(trimethylsilyl)amino)phenyl)-4-hydroxypiperidine-1-carboxylate was treated with a solution of tetrabutylammonium fluoride (1M THF, 40 mL) at room temperature for 1 hour. The reaction mixture was diluted with water and extracted with ethyl acetate. The organics were washed with water and brine, dried with magnesium sulfate, filtered and concentrated. Purification by normal phase chromatography provided the title compound.

Workup

  1. stirringThe reaction mixture was stirred at −78° C. for 30 minutes
  2. temperaturewarmed to room temperature
  3. customThe reaction was quenched by addition of saturated ammonium chloride solution (100 mL)
  4. extractionwas extracted with ethyl acetate
  5. washThe combined organics were washed with water, brine
  6. dry with materialdried with magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. additionThe crude tert-butyl 4-(4-(bis(trimethylsilyl)amino)phenyl)-4-hydroxypiperidine-1-carboxylate was treated with a solution of tetrabutylammonium fluoride (1M THF, 40 mL) at room temperature for 1 hour
  10. additionThe reaction mixture was diluted with water
  11. extractionextracted with ethyl acetate
  12. washThe organics were washed with water and brine
  13. dry with materialdried with magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customPurification by normal phase chromatography

Sources & evidence

ORD record
ord-70422c169aee44f7a411421450bda329
Source dataset
uspto-grants-2015_03
Patent number
US08975398B2

Reaction notes

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