3-(Chloromethyl)pyridine hydrochloride → (S)-tert-butyl 2-oxo-1-(pyridin-3-ylmethyl)azepan-3-ylcarbamate

HRID 529500Notes

Reaction equation

HRID 529500 reaction equation
[O:1]=[C:2]1[C@@H:8]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:7][CH2:6][CH2:5][CH2:4][NH:3]1.[H-].[Na+].Cl.Cl[CH2:21][C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1>CN(C=O)C>[O:1]=[C:2]1[C@@H:8]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:13])([CH3:15])[CH3:14])[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[CH2:21][C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1

Participants

5

Reactant 3

HCID 233943-(Chloromethyl)pyridine hydrochlorideHCID 24758Sodium hydrideHCID 7022178(S)-tert-Butyl (2-oxoazepan-3-yl)carbamate

Product 1

HCID 68309880(S)-tert-butyl 2-oxo-1-(pyridin-3-ylmethyl)azepan-3-ylcarbamateYield 48.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (S)-tert-butyl 2-oxoazepan-3-ylcarbamate (230 mg, 1.01 mmol) in DMF (1 mL) was added sodium hydride (129 mg, 3.22 mmol) at rt under argon. The reaction mixture was stirred at rt for 10 min followed by the addition of 3-(chloromethyl)pyridine hydrochloride (197 mg, 1.54 mmol) at rt. The reaction was allowed to stir at rt for an additional 30 min. The reaction was quenched with water and extracted with EtOAc. The organic layer was washed with water, saturated aqueous NaCl, dried over MgSO4, filtered and concentrated. The crude product was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-80% EtOAc/Hex to give (S)-tert-butyl 2-oxo-1-(pyridin-3-ylmethyl)azepan-3-ylcarbamate (155 mg, 0.485 mmol, 48.2% yield) as colorless oil. Anal. Calcd. for C17H25N3O3 m/z 319.4. found: 320.2 (M+H)+.

Workup

  1. stirringto stir at rt for an additional 30 min
  2. customThe reaction was quenched with water
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with water, saturated aqueous NaCl
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified
  9. washeluting with a gradient of 0-80% EtOAc/Hex

Sources & evidence

ORD record
ord-9bf26b59efde4e3f9da955af56f8bea0
Source dataset
uspto-grants-2016_05
Patent number
US09346852B2

Reaction notes

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