Tert-butyl 4-hydroxypiperidine-1-carboxylate → Tert-butyl 4-[(6-chloro-5-methylpyrimidin-4-yl)oxy]piperidine-1-carboxylate

HRID 448572Notes

Reaction equation

HRID 448572 reaction equation
Cl[C:2]1[C:7]([CH3:8])=[C:6]([Cl:9])[N:5]=[CH:4][N:3]=1.[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][CH:20]([OH:23])[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11].CC(C)([O-])C.[K+]>C1COCC1>[C:10]([O:14][C:15]([N:17]1[CH2:22][CH2:21][CH:20]([O:23][C:2]2[C:7]([CH3:8])=[C:6]([Cl:9])[N:5]=[CH:4][N:3]=2)[CH2:19][CH2:18]1)=[O:16])([CH3:13])([CH3:11])[CH3:12]

Participants

5

Reactant 3

HCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 8188604,6-Dichloro-5-methylpyrimidineHCID 23665647Potassium tert-butoxide

Product 1

HCID 59566479Tert-butyl 4-[(6-chloro-5-methylpyrimidin-4-yl)oxy]piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4,6-dichloro-5-methyl-pyrimidine (8.15 g, 50 mmol) in 200 mL of THF, was added 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (10 g, 1 eq) and potassium tert-butoxide (6.1 g, 1.2 eq) at 0° C. The resulting mixture was stirred at room temperature for 16 h then quenched with a saturated solution of NH4Cl and extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over magnesium sulfate and concentrated to give crude 9a.

Workup

  1. customthen quenched with a saturated solution of NH4Cl
  2. extractionextracted with ethyl acetate
  3. washThe combined organic layers were washed with water and brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-4507770d5af6447cb143964b296b4a65
Source dataset
uspto-grants-2013_07
Patent number
US08481731B2

Reaction notes

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