Water → 4-Hydroxypiperidine-1-carbonitrile

HRID 1036798Notes

Reaction equation

HRID 1036798 reaction equation
C(=O)(O)[O-].[Na+].O.[OH:7][CH:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1.[N:14]#[C:15]Br>C(Cl)Cl>[C:15]([N:11]1[CH2:12][CH2:13][CH:8]([OH:7])[CH2:9][CH2:10]1)#[N:14]

Participants

6

Reactant 4

HCID 962WaterHCID 10476Cyanogen BromideHCID 79341Piperidin-4-olHCID 516892Sodium Bicarbonate

Product 1

HCID 218978254-Hydroxypiperidine-1-carbonitrileYield 91%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A 5-liter, 3-neck flask was equipped with mechanical stirring, a reflux condenser, and a powder addition funnel. Sodium bicarbonate (840 g, 10 mmol) was added via the powder funnel while stirring, then water (ca. 300-400 mL) was gradually added while vigorously stirring to form a thick, uniform slurry. The flask was then placed in an ice bath, and a solution of 4-hydroxypiperidine (506 g, 5.00 mol) in CH2Cl2 (1.0 L) was added, and the contents were vigorously mixed while cooling. A solution of cyanogen bromide (640 g, 6.0 mol) in CH2Cl2 (600 mL) was added in a dropwise fashion over 2 h, and stirring was continued for an additional 30 min. The ice bath was removed, and the mechanical stirrer was replaced by a magnetic stirrer, and the reaction mixture was stirred for 16 h. The flask was once again placed under mechanical stirring, and sodium carbonate (100 g) was added in order to ensure complete neutralization. MgSO4 (500 g) was added, and vigorous stirring was continued for 15 min. The resulting suspension was filtered, rinsing with CH2Cl2 (2.0 L). A light amber, viscous oil was obtained upon solvent removal to give 1-cyano-4-hydroxypiperidine (574 g, 91% yield. 1H NMR (CDCl3) δ 3.80 (m, 1 H), 3.39 (m, 2 H), 3.05 (m, 2 H), 1.87 (m, 2 H), 1.70 (br s, 1 H), 1.62 (m, 2 H), MS m/z 212.1 (M+).

Workup

  1. customA 5-liter, 3-neck flask was equipped with mechanical stirring, a reflux condenser, and a powder addition funnel
  2. stirringwhile vigorously stirring
  3. customto form a thick, uniform slurry
  4. customThe flask was then placed in an ice bath
  5. additionthe contents were vigorously mixed
  6. temperaturewhile cooling
  7. stirringstirring
  8. customThe ice bath was removed
  9. customthe mechanical stirrer was replaced by a magnetic stirrer
  10. stirringthe reaction mixture was stirred for 16 h
  11. additionwas added in order
  12. additionMgSO4 (500 g) was added
  13. stirringvigorous stirring
  14. waitwas continued for 15 min
  15. filtrationThe resulting suspension was filtered
  16. washrinsing with CH2Cl2 (2.0 L)
  17. customA light amber, viscous oil was obtained upon solvent removal

Sources & evidence

ORD record
ord-92e66eea2b1f4a04aafd778d94766bb5
Source dataset
uspto-grants-2013_10
Patent number
US08546429B2

Reaction notes

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