4,6-Dichloro-5-methylpyrimidine → 4-(6-Chloro-5-methyl-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester

HRID 2377898Notes

Reaction equation

HRID 2377898 reaction equation
[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([OH:13])[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].[Cl:14][C:15]1[C:20]([CH3:21])=[C:19](Cl)[N:18]=[CH:17][N:16]=1>C1COCC1.CC(C)([O-])C.[K+]>[CH:1]([O:4][C:5]([N:7]1[CH2:8][CH2:9][CH:10]([O:13][C:19]2[C:20]([CH3:21])=[C:15]([Cl:14])[N:16]=[CH:17][N:18]=2)[CH2:11][CH2:12]1)=[O:6])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 8188604,6-Dichloro-5-methylpyrimidineHCID 16745126Isopropyl 4-Hydroxypiperidine-1-carboxylate

Product 1

HCID 114933574-(6-Chloro-5-methyl-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl esterYield 98.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 23665647Potassium tert-butoxideSolvent

Procedure

To a solution of 4-hydroxy-piperidine-1-carboxylic acid isopropyl ester (6.26 g, 33.4 mmol) and 4,6-dichloro-5-methyl-pyrimidine (5.45 g, 33.4 mmol) in 100 mL THF, 1M potassium tert-butoxide in THF (40 mL, 40 mmol) were added slowly by syringe pump. After 1 hour, everything had been added and mixture was concentrated. Residue was extracted with methylene chloride and water. Organic phases were dried over magnesium sulfate, filtered, and concentrated to give 4-(6-chloro-5-methyl-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester as a pale yellow solid (10.3 g, 98%). 1H NMR (CDCl3, 400 MHz) δ 1.22-1.24 (d, 6H), 1.74-1.81 (m, 2H), 1.95-2.04 (m, 2H), 2.24 (s, 3H), 3.40-3.45 (m, 2H), 3.74-3.81 (m, 2H), 4.90-4.98 (m, 1H), 5.31-5.37 (m, 1H), 8.40 (s, 1H).

Workup

  1. additioneverything had been added
  2. concentrationmixture was concentrated
  3. extractionResidue was extracted with methylene chloride and water
  4. dry with materialOrganic phases were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-554f767dae854babba2a74a731370cc8
Source dataset
uspto-grants-2008_12
Patent number
US07470699B2

Reaction notes

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