Pyridine → 1,1-Dimethylethyl 4-[5-(chloromethyl)-1,2,4-oxadiazol-3-yl]piperazine-1-carboxylate

HRID 244577Notes

Reaction equation

HRID 244577 reaction equation
O[CH2:2][C:3]1[O:7][N:6]=[C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[N:4]=1.[Cl:21]CCl.N1C=CC=CC=1.S(Cl)(Cl)=O>C(OCC)(=O)C>[Cl:21][CH2:2][C:3]1[O:7][N:6]=[C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[N:4]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 6344DichloromethaneHCID 24386Thionyl ChlorideHCID 666729771,1-Dimethylethyl 4-[5-(hydroxymethyl)-1,2,4-oxadiazol-3-yl]piperazine-1-carboxylate

Product 1

HCID 666739121,1-Dimethylethyl 4-[5-(chloromethyl)-1,2,4-oxadiazol-3-yl]piperazine-1-carboxylateYield 61%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

1,1-Dimethylethyl 4-[5-(hydroxymethyl)-1,2,4-oxadiazol-3-yl]piperazine-1-carboxylate (7.4 g, 26 mmol) was taken into dichloromethane (100 mL) followed by addition of pyridine (5.3 mL, 65 mmol) and the solution was cooled to 0° C. Thionyl chloride (2.3 mL, 31.2 mmol) was added by syringe and the mixture was allowed to warm to room temperature and stirred an additional 12 hours. The mixture was then concentrated in vacuo and the residue partitioned with ethyl acetate and water. The aqueous phase was extracted twice with ethyl acetate and the combined organic layers were washed once with 0.1M aqueous hydrochloric acid then saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. Filtration, concentration and purification of the residue by silica gel flash chromatography using 3:1 hexanes:ethyl acetate provided 1,1-dimethylethyl 4-[5-(chloromethyl)-1,2,4-oxadiazol-3-yl]piperazine-1-carboxylate (4.82 g, 61% yield) as a slightly yellow crystalline solid. 1H-NMR (400 MHz, CDCl3): 4.53 (s, 2H), 3.51 (tr, 4H), 3.43 (tr, 4H), 1.48 (s, 9H).

Workup

  1. temperatureto warm to room temperature
  2. concentrationThe mixture was then concentrated in vacuo
  3. customthe residue partitioned with ethyl acetate and water
  4. extractionThe aqueous phase was extracted twice with ethyl acetate
  5. washthe combined organic layers were washed once with 0.1M aqueous hydrochloric acid
  6. dry with materialsaturated aqueous sodium chloride and dried over anhydrous magnesium sulfate
  7. filtrationFiltration, concentration and purification of the residue by silica gel flash chromatography

Sources & evidence

ORD record
ord-fedfc3d4539041a9b7477c47f6c20060
Source dataset
uspto-grants-2014_02
Patent number
US08658654B2

Reaction notes

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