Cyanogen Bromide → 4-Hydroxypiperidine-1-carbonitrile

HRID 1931592Notes

Reaction equation

HRID 1931592 reaction equation
C(=O)(O)[O-].[Na+].[OH:6][CH:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1.[N:13]#[C:14]Br>O.ClCCl>[OH:6][CH:7]1[CH2:12][CH2:11][N:10]([C:14]#[N:13])[CH2:9][CH2:8]1

Participants

6

Reactant 3

HCID 10476Cyanogen BromideHCID 79341Piperidin-4-olHCID 516892Sodium Bicarbonate

Product 1

HCID 218978254-Hydroxypiperidine-1-carbonitrileYield 84%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
4 °C

Procedure

A slurry of sodium bicarbonate (24.9 g, 296 mmol) in water (15 mL) was cooled in an ice-bath and a solution of 4-hydroxypiperidine (15 g, 148 mmol) in dichloromethane (25 mL) was added. With rapid stirring, a solution of cyanogen bromide (18.8 g, 177 mmol) in dichloromethane (25 mL) was added dropwise over 15 min. The reaction was stirred for 30 min at ˜4° C., then the cooling bath was removed and the reaction mixture was stirred overnight at room temperature. Sodium carbonate (3 g) and magnesium sulfate (15 g) were added and the mixture was stirred for 30 min, and then filtered. The solids were washed with dichloromethane (50 mL) and the solvents were evaporated from the combined filtrate and washings to give 4-hydroxy-piperidine-1-carbonitrile (15.6 g, 84%) which was used directly in the subsequent step without further purification.

Workup

  1. customthe cooling bath was removed
  2. stirringthe reaction mixture was stirred overnight at room temperature
  3. additionSodium carbonate (3 g) and magnesium sulfate (15 g) were added
  4. stirringthe mixture was stirred for 30 min
  5. filtrationfiltered
  6. washThe solids were washed with dichloromethane (50 mL)
  7. customthe solvents were evaporated from the combined filtrate and washings

Sources & evidence

ORD record
ord-641e1673e6c542fdba4fac96173eb90c
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

Loading…