1,2-Dichloroethane → (R)-3-(3-chloro-4-isopropoxyphenyl)-5-(4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)phenyl)-1,2,4-oxadiazole

HRID 1172941Notes

Reaction equation

[CH3:1][C:2]1([CH3:18])[O:6][C@H:5]([CH2:7][O:8][C:9]2[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][CH:10]=2)[CH2:4][O:3]1.C(Cl)CCl.C1C=C2N=NN(O)C2=CC=1.O.[Cl:34][C:35]1[CH:36]=[C:37]([CH:42]=[CH:43][C:44]=1[O:45][CH:46]([CH3:48])[CH3:47])/[C:38](=[N:40]/O)/[NH2:39]>CN(C=O)C>[Cl:34][C:35]1[CH:36]=[C:37]([C:38]2[N:40]=[C:13]([C:12]3[CH:11]=[CH:10][C:9]([O:8][CH2:7][C@@H:5]4[CH2:4][O:3][C:2]([CH3:1])([CH3:18])[O:6]4)=[CH:17][CH:16]=3)[O:15][N:39]=2)[CH:42]=[CH:43][C:44]=1[O:45][CH:46]([CH3:48])[CH3:47]

Participants

Conditions

Temperature: 140 °C

Procedure

To a slurry of (R)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)benzoic acid (0.303 g, 1.203 mmol) in DMF (1.367 ml) was added EDC (0.231 g, 1.203 mmol) followed by HOBT hydrate (0.163 g, 1.203 mmol). After about 1.5 h a solution of (Z)-3-chloro-N′-hydroxy-4-isopropoxybenzimidamide (0.250 g, 1.09 mmol) in DMF (1.367 ml) was added. The reaction mixture was heated to about 140° C. for about 2 hrs. After cooling to room temperature the reaction mixture was concentrated in vacuo and purified by chromatography on silica gel (eluting with EtOAc/Hep) to provide (R)-3-(3-chloro-4-isopropoxyphenyl)-5-(4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)phenyl)-1,2,4-oxadiazole (0.339 g, 70%) as a colorless solid. LCMS (Table 1, Method c) Rt=3.36 min, m/z 445 (M+H)+.

Workup

temperatureAfter cooling to room temperature the reaction mixture
concentrationwas concentrated in vacuo
custompurified by chromatography on silica gel (eluting with EtOAc/Hep)

Sources & evidence

ORD record: ord-ef43adc331634daeb1c61aa29f40f087
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07834039B2

Reaction notes

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