4-Cyanopiperidine → HCID 89579310, compound

HRID 714543Notes

Reaction equation

HRID 714543 reaction equation
[C:1]([CH:3]1[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1)#[N:2].[CH2:9]([O:11][C:12]([N:14]1[CH2:20][CH2:19][CH2:18][C:17](=O)[CH2:16][CH2:15]1)=[O:13])[CH3:10].C([BH3-])#N.[Na+]>CO.[Cl-].[Zn+2].[Cl-]>[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([CH:17]2[CH2:18][CH2:19][CH2:20][N:14]([C:12]([O:11][CH2:9][CH3:10])=[O:13])[CH2:15][CH2:16]2)[CH2:5][CH2:4]1)#[N:2]

Participants

6

Reactant 3

HCID 1382234-CyanopiperidineHCID 5003444Sodium cyanoborohydrideHCID 126660861-Carbethoxyazepan-4-one

Product 1

HCID 89579310HCID 89579310, compoundYield 8.9%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

4-cyanopiperidine (0.40 g, 3.62 mmol) was dissolved in MeOH (15 mL), 4-oxoazepane-1-carboxylic acid ethyl ester (0.672 g, 3.62 mmol) and zinc chloride (1.98 g, 14.48 mmol) were added. The reaction mixture was heated for 2 h at 50° C. The solution was then cooled on ice and treated portionwise with sodium cyanoborohydride (0.456 g, 7.24 mmol) and reheated to 50° C. overnight. The reaction mixture was concentrated in vacuo to a white solid. This was dissolved in sat. NH4Cl sol. and extracted with EtOAc (3×50 mL). The combined organics were washed with sat. NaCl sol., dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 25 g, 40-63 μm, 60 Å, 50 mL per min, gradient 0% to 4% MeOH in DCM]) to give ethyl 4-(4-cyanopiperidin-1-yl)azepane-1-carboxylate as an oil (0.090 g, 8.9%).

Workup

  1. temperatureThe solution was then cooled on ice
  2. concentrationThe reaction mixture was concentrated in vacuo to a white solid
  3. dissolutionThis was dissolved in sat. NH4Cl sol.
  4. extractionextracted with EtOAc (3×50 mL)
  5. washThe combined organics were washed with sat. NaCl sol.
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 25 g, 40-63 μm, 60 Å, 50 mL per min, gradient 0% to 4% MeOH in DCM])

Sources & evidence

ORD record
ord-0d52c3c41619456a9f79845346adbb88
Source dataset
uspto-grants-2015_11
Patent number
US09187451B2

Reaction notes

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