4,6-Dichloropyrimidine → tert-Butyl 4-[(6-chloropyrimidin-4-yl)oxy]piperidine-1-carboxylate

HRID 448558Notes

Reaction equation

HRID 448558 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[K+].[Cl:21][C:22]1[CH:27]=[C:26](Cl)[N:25]=[CH:24][N:23]=1.C(=O)(O)[O-].[Na+]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:26]2[CH:27]=[C:22]([Cl:21])[N:23]=[CH:24][N:25]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 709434,6-DichloropyrimidineHCID 516892Sodium BicarbonateHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 21906116tert-Butyl 4-[(6-chloropyrimidin-4-yl)oxy]piperidine-1-carboxylateYield 51.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (3.1 g, 15.5 mmol) and potassium tert-butoxide (1.74 g, 1 eq) in 20 mL THF at 0° C., was added 4,6-dichloropyrimidine (2.3 g, 1 eq). The reaction mixture was stirred for 1 h then a solution of saturated sodium bicarbonate was added. The aqueous layer was extracted with ethyl acetate twice and the combined extracts were washed with a solution of saturated sodium bicarbonate, dried over magnesium sulfate and evaporated. The residue was purified on silica gel (eluent: 20% ethyl acetate in hexane) to give 2.49 g (51% yield) of 3a.

Workup

  1. extractionThe aqueous layer was extracted with ethyl acetate twice
  2. washthe combined extracts were washed with a solution of saturated sodium bicarbonate
  3. dry with materialdried over magnesium sulfate
  4. customevaporated
  5. customThe residue was purified on silica gel (eluent: 20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-5b881f820a154d7ca36add26e3d7fc7c
Source dataset
uspto-grants-2013_07
Patent number
US08481731B2

Reaction notes

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