Isopropyl 4-Hydroxypiperidine-1-carboxylate → HCID 86597367, compound

HRID 2377928Notes

Reaction equation

HRID 2377928 reaction equation
Cl[C:2]1[C:7]([CH:8]2[CH2:10][CH2:9]2)=[C:6]([Cl:11])[N:5]=[CH:4][N:3]=1.[CH:12]([O:15][C:16]([N:18]1[CH2:23][CH2:22][CH:21]([OH:24])[CH2:20][CH2:19]1)=[O:17])([CH3:14])[CH3:13].CC(C)([O-])C.[K+]>C1COCC1>[CH:12]([O:15][C:16]([N:18]1[CH2:19][CH2:20][CH:21]([O:24][C:2]2[C:7]([CH:8]3[CH2:10][CH2:9]3)=[C:6]([Cl:11])[N:5]=[CH:4][N:3]=2)[CH2:22][CH2:23]1)=[O:17])([CH3:14])[CH3:13]

Participants

5

Reactant 3

HCID 16745126Isopropyl 4-Hydroxypiperidine-1-carboxylateHCID 23665647Potassium tert-butoxideHCID 544142814,6-Dichloro-5-cyclopropylpyrimidine

Product 1

HCID 86597367HCID 86597367, compoundYield 73.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4,6-dichloro-5-cyclopropyl-pyrimidine (700 mg, 3.70 mmol) and 4-hydroxy-piperidine-1-carboxylic acid isopropyl ester (636.6 mg, 3.70 mmol) in dry THF under nitrogen at 0° C., potassium tert-butoxide (1M solution in THF, 4.45 mL) was added dropwise. The reaction was stirred at rt for 30 min. The mixture was quenched with water and extracted with EtOAc (3×). The organic layer was washed with water, sat. NH4Cl and brine, followed by drying over sodium sulfate and concentration under vacuo. The resulting oil was purified by flash chromatography (0-20% EtOAc/Hexanes) to afford 4-(6-chloro-5-cyclopropyl-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester (0.927 g, 73.7%) as colorless oil. Exact mass calculated for C16H22ClN3O3 339.13, found 340.3 (MH+).

Workup

  1. customThe mixture was quenched with water
  2. extractionextracted with EtOAc (3×)
  3. washThe organic layer was washed with water, sat. NH4Cl and brine
  4. dry with materialby drying over sodium sulfate and concentration under vacuo
  5. customThe resulting oil was purified by flash chromatography (0-20% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-2fcc42f47a894aadb3a7bb7fa154895c
Source dataset
uspto-grants-2008_12
Patent number
US07470699B2

Reaction notes

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