Cyanogen Bromide → 4-[(1R)-1-hydroxyethyl]-1-piperidinecarbonitrile

HRID 423707Notes

Reaction equation

HRID 423707 reaction equation
C(O)(=O)C.[NH:5]1[CH2:10][CH2:9][CH:8]([C@H:11]([OH:13])[CH3:12])[CH2:7][CH2:6]1.C([O-])(=O)C.[Na+].[N:19]#[C:20]Br>CO.C(Cl)Cl>[OH:13][C@@H:11]([CH:8]1[CH2:9][CH2:10][N:5]([C:20]#[N:19])[CH2:6][CH2:7]1)[CH3:12]

Participants

6

Reactant 3

HCID 10476Cyanogen BromideHCID 517045Sodium AcetateHCID 66673151(1r)-1-(4-Piperidinyl)ethanol acetic acid salt

Product 1

HCID 866387534-[(1R)-1-hydroxyethyl]-1-piperidinecarbonitrileYield 103.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

(1R)-1-(4-Piperidinyl)ethanol acetic acid salt (Example 167, Step 1, 568 mg, 3 mmol, 94% ee) and sodium acetate (2.46 g, 30 mmol) in MeOH (30 mL) was stirred at room temperature for 15 min. A solution of cyanogen bromide (953 mg, 9 mmol) in CH2Cl2 (4 mL) was added at 0° C. The mixture was stirred from 0° C. to 25° C. for 12 h. The salt was removed by filtration and washed by CH2Cl2. After concentration, the crude product was purified by chromatography on a silica gel column using 70% EtOAc/CH2Cl2 to give 480 mg (99%) of 4-[(1R)-1-hydroxyethyl]-1-piperidinecarbonitrile as an oil. 1H NMR (400 MHz, CDCl3): δ 3.69 (s, 1H), 3.67-3.57 (m, 1H), 3.54-3.43 (m, 2H), 3.08-2.94 (m, 2H), 1.96-1.84 (m, 1H), 1.67-1.65 (m, 1H), 1.53-1.35 (m, 3H), 1.20 (d, 3H, J=6.3 Hz).

Workup

  1. customThe salt was removed by filtration
  2. washwashed by CH2Cl2
  3. concentrationAfter concentration
  4. customthe crude product was purified by chromatography on a silica gel column

Sources & evidence

ORD record
ord-b7788a5d180449a7a7c526e32a11f7e1
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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