Sodium hydride → tert-Butyl 4-((2-chloropyrimidin-4-yl)oxy)piperidine-1-carboxylate

HRID 530373Notes

Reaction equation

HRID 530373 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[H-].[Na+].[Cl:17][C:18]1[N:23]=[C:22](Cl)[CH:21]=[CH:20][N:19]=1>CN(C=O)C.C(OCC)(=O)C>[Cl:17][C:18]1[N:23]=[C:22]([O:1][CH:2]2[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]2)[CH:21]=[CH:20][N:19]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 775312,4-DichloropyrimidineHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

Product 1

HCID 71629906tert-Butyl 4-((2-chloropyrimidin-4-yl)oxy)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

tert-Butyl 4-hydroxypiperidine-1-carboxylate (1.00 g, 4.97 mmol) was added to a suspension of sodium hydride (60 wt %, 0.238 g, 5.96 mmol) in DMF (16.56 mL) and stirred for 30 minutes at room temperature. 2,4-Dichloropyrimidine (1.11 g, 7.45 mmol) was added to the reaction mixture and stirred for 2 hours at room temperature. The mixture was then diluted with ethyl acetate (100 mL) and washed with 1:1 water:brine (3×). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (ethyl acetate/hexanes) provided tert-butyl 4-[(2-chloropyrimidin-4-yl)oxy]piperidine-1-carboxylate as a colorless oil.

Workup

  1. stirringstirred for 2 hours at room temperature
  2. washwashed with 1:1 water
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-eff35e3ce5264ebdbbb42eddd6381e59
Source dataset
uspto-grants-2016_05
Patent number
US09353066B2

Reaction notes

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