Triethylamine → N-(4-(benzyloxy)pyridin-3-yl)methanesulfonamide

HRID 595691Notes

Reaction equation

HRID 595691 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]=[CH:11][C:10]=1[NH2:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(CC)CC.[CH3:23][S:24](Cl)(=[O:26])=[O:25].O[Li].O>C(Cl)Cl.CCOC(C)=O.O>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]=[CH:11][C:10]=1[NH:15][S:24]([CH3:23])(=[O:26])=[O:25])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 168937Lithium hydroxide, monohydrateHCID 288900524-(Benzyloxy)pyridin-3-amine

Product 1

HCID 59233662N-(4-(benzyloxy)pyridin-3-yl)methanesulfonamideYield 54%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(benzyloxy)pyridin-3-amine (40 g, 0.2 mol) and Et3N (60.6 g, 0.6 mol) in DCM (600 mL), MsCl (45.8 g, 0.4 mol) was added dropwise at 0° C. The mixture was allowed to warm up to room temperature and stirred overnight. The reaction mixture was quenched with NaHCO3 and extracted with DCM. The organic phase was washed with brine, dried over Na2SO4, and concentrated. The residue was dissolved in THF:H2O=5:1 (500 mL) and LiOH.H2O (16.8 g, 0.4 mmol) was added. The mixture was stirred for 4 hours at room temperature. EtOAc (300 mL) was added, and the organic phase washed with NaHCO3 (sat., a.q.), brine, dried over Na2SO4, filtrated and concentrated to give pure N-(4-(benzyloxy)pyridin-3-yl)methanesulfonamide (30.0 g, yield: 54.0%). 1H-NMR (CDCl3, 400 MHz) δ 8.67 (s, 1H), 8.34 (d, J=5.6 Hz, 1H), 7.35˜7.42 (m, 5H), 6.91 (d, J=5.6 Hz, 1H), 6.61 (br, 1H), 5.15 (s, 2H), 2.96 (s, 3H). MS (M+H)+: 279.

Workup

  1. customThe reaction mixture was quenched with NaHCO3
  2. extractionextracted with DCM
  3. washThe organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in THF
  7. stirringThe mixture was stirred for 4 hours at room temperature
  8. washthe organic phase washed with NaHCO3 (sat., a.q.), brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltrated
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-cc2cd0b0de67426a9ba7918ac4d946af
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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