Cyanogen Bromide → 4-(Hydroxymethyl)piperidine-1-carbonitrile

HRID 423542Notes

Reaction equation

HRID 423542 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][OH:8])[CH2:3][CH2:2]1.C([O-])(O)=O.[Na+].[N:14]#[C:15]Br>C(Cl)Cl.O>[OH:8][CH2:7][CH:4]1[CH2:5][CH2:6][N:1]([C:15]#[N:14])[CH2:2][CH2:3]1

Participants

6

Reactant 3

HCID 10476Cyanogen BromideHCID 4207714-PiperidinemethanolHCID 516892Sodium Bicarbonate

Product 1

HCID 513582894-(Hydroxymethyl)piperidine-1-carbonitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 4-piperidinemethanol (140 g, 1.22 mol) in CH2Cl2 (1 L) was treated with a slurry of NaHCO3 (205 g, 2.44 mol) in water (1.4 L) at 0° C. The mixture was stirred at 0° C. for 15 min, and then charged with a solution of cyanogen bromide in CH2Cl2, (1.34 mol) at 0° C. The reaction mixture was stirred and allowed to warm to ambient temperature, and stirred overnight. The aqueous layer was separated and extracted with CH2Cl2. The combined organic extracts were dried over Na2SO4, filtered, and the filtrate was concentrated. The crude product was combined with other batches made similarly and purified by chromatography on a silica gel column to give 300 g of 4-(hydroxymethyl)-1-piperidinecarbonitrile.

Workup

  1. stirringThe reaction mixture was stirred
  2. temperatureto warm to ambient temperature
  3. stirringstirred overnight
  4. customThe aqueous layer was separated
  5. extractionextracted with CH2Cl2
  6. dry with materialThe combined organic extracts were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated
  9. custompurified by chromatography on a silica gel column

Sources & evidence

ORD record
ord-c5ce960f46ee40f6b88af0a06f154805
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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