Potassium Carbonate → 1-{[3-(Propan-2-yl)-1,2,4-oxadiazol-5-yl]methyl}pyrrolidin-3-ol

HRID 1864124Notes

Reaction equation

Cl[CH2:2][C:3]1[O:7][N:6]=[C:5]([CH:8]([CH3:10])[CH3:9])[N:4]=1.[OH:11][CH:12]1[CH2:16][CH2:15][NH:14][CH2:13]1.C([O-])([O-])=O.[K+].[K+]>CC#N>[OH:11][CH:12]1[CH2:16][CH2:15][N:14]([CH2:2][C:3]2[O:7][N:6]=[C:5]([CH:8]([CH3:10])[CH3:9])[N:4]=2)[CH2:13]1

Participants

Conditions

Temperature: 65 °C

Procedure

A mixture of 5-chloromethyl-3-isopropyl-[1,2,4]oxadiazole (1.6 g, 10 mmol) and (RS)-3-hydroxypyrrolidine (960 mg, 11 mmol) were combined neat, diluted with MeCN (10 mL), and K2CO3 (2.75 g, 20 mmol) was added. The mixture was heated at 65° C. for 1 h, and was filtered upon cooling. The solvent was removed and the residue was taken up in CH2Cl2 and rinsed with water. The organic extract was dried over MgSO4, the solvent was removed, and the residue was taken up in ether and filtered in order to remove a small amount of quaternary ammonium byproduct. Solvent removal from the filtrate gave (RS)-3-hydroxy-1-[(3-isopropyl-1,2,4-oxadiazol-5-yl)methyl]pyrrolidine as an amber oil (1.72 g, 82% yield): 1H NMR (DMSO-d6) δ 4.76 (d, 1H, J=4.5 Hz), 4.19 (m, 1H), 3.90 (s, 2H), 3.05 (m, 1H), 2.79 (m, 1H), 2.69 (m, 1H), 2.53 (m, 1H), 2.43 (m, 1H), 1.98 (m, 1H), 1.54 (m, 1H), 1.25 (d, 6H, J=6.8 Hz); MS m/z 212.1 (M+).

Workup

additionwas added
filtrationwas filtered
temperatureupon cooling
customThe solvent was removed
washrinsed with water
extractionThe organic extract
dry with materialwas dried over MgSO4
customthe solvent was removed
filtrationfiltered in order
customto remove a small amount of quaternary ammonium byproduct
customSolvent removal from the filtrate

Sources & evidence

ORD record: ord-8e0c4edd3f7a44eb97219e17e86a43a6
Source dataset: uspto-grants-2009_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07625906B2

Reaction notes

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