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

HRID 2207415Notes

Reaction equation

HRID 2207415 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>C1COCC1.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 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

tert-Butyl 4-hydroxypiperidine-1-carboxylate (500 mg, 2.48 mmol) was added to a suspension of sodium hydride (60%, 149 mg, 3.73 mmol) in THF (8.28 mL) and the mixture was stirred for 30 minutes at room temperature. 2,4-Dichloropyrimidine (333 mg, 2.24 mmol) was added to the reaction mixture at 0° C. and warmed to room temperature over 3 days. The mixture was diluted with ethyl acetate (20.0 mL), and then washed with water:brine 1:1 (3×40 mL). The organic extracts were dried (Na2SO4) and concentrated in vacuo. The residue was purified by silica gel chromatography (10-60% ethyl acetate in hexanes) to yield tert-butyl 4-[(2-chloropyrimidin-4-yl)oxy]piperidine-1-carboxylate. MS APCI calc'd for C14H21ClN3O3 [M+H]+ 314. found 314.

Workup

  1. temperaturewarmed to room temperature over 3 days
  2. washwashed with water:brine 1:1 (3×40 mL)
  3. dry with materialThe organic extracts were dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel chromatography (10-60% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-16e8dfa7d0b6448680a0f7550c7056da
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

Loading…