Sodium hydride → tert-butyl 6-bromopyridin-2-yl((4-methoxytetrahydro-2H-pyran-4-yl)methyl)carbamate

HRID 1623261Notes

Reaction equation

HRID 1623261 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH:5]=[CH:4][CH:3]=1.[H-].[Na+].CC1C=CC(S(O[CH2:29][C:30]2([O:36][CH3:37])[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)(=O)=O)=CC=1>CN(C=O)C.C(OCC)(=O)C>[Br:1][C:2]1[N:7]=[C:6]([N:8]([CH2:29][C:30]2([O:36][CH3:37])[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)[C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13])[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 13040380Tert-butyl (6-bromopyridin-2-YL)carbamateHCID 58127128HCID 58127128, compound2×

Product 1

HCID 58127385tert-butyl 6-bromopyridin-2-yl((4-methoxytetrahydro-2H-pyran-4-yl)methyl)carbamateYield 46%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tert-butyl 6-bromo-pyridin-2-ylcarbamate (136 mg, 0.50 mmol) in DMF (2 ml) under nitrogen was added NaH (60%, 40 mg, 1.0 mmol) under stirring. The resultant mixture was stirred at room temperature for one hour. A solution of (4-methoxytetrahydro-2H-pyran-4-yl)methyl 4-methylbenzenesulfonate (Intermediate 0, 152 mg, 0.506 mmol) in DMF (1.5 ml) was then added. The resulting mixture was then stirred at 85° C. for about 18 hours. The mixture was diluted with 30 ml of ethyl acetate, washed with water (20 ml×3) and dried with sodium sulfate. After concentration the residue was purified by silica gel chromatography using a 12 g column, eluting with 5-20% ethyl acetate in hexane to give the desired title compound as a viscous oil (92 mg, 46% yield), which solidified upon standing overnight. LCMS (m/z): 403.1 [M+H]+; Rt=1.026 min.

Workup

  1. stirringThe resulting mixture was then stirred at 85° C. for about 18 hours
  2. washwashed with water (20 ml×3)
  3. dry with materialdried with sodium sulfate
  4. concentrationAfter concentration the residue
  5. customwas purified by silica gel chromatography
  6. washeluting with 5-20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-61b0f4d77f3f4b65afada238d57c1a53
Source dataset
uspto-grants-2014_07
Patent number
US08778951B2

Reaction notes

Loading…