Ethyl bromoacetate → Ethyl (3-{3-[4-(2-bromo-5-fluorophenoxy)piperidin-1-yl]-1,2,4-oxadiazol-5-yl}-1H-pyrrol-1-yl)acetate

HRID 561216Notes

Reaction equation

[Br:1][C:2]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:3]=1[O:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[N:15]=[C:14]([C:16]3[CH:20]=[CH:19][NH:18][CH:17]=3)[O:13][N:12]=2)[CH2:7][CH2:6]1.[H-].[Na+].Br[CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31]>CN(C=O)C>[Br:1][C:2]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:3]=1[O:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11]2[N:15]=[C:14]([C:16]3[CH:20]=[CH:19][N:18]([CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH:17]=3)[O:13][N:12]=2)[CH2:7][CH2:6]1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 4-(2-bromo-5-fluorophenoxy)-1-[5-(1H-pyrrol-3-yl)-1,2,4-oxadiazol-3-yl]piperidine (60 mg, 0.15 mmol) in DMF (491 μL) was added sodium hydride (11.8 mg, 0.3 mmol). After 5 min, ethyl bromoacetate (25 μL, 0.22 mmol) was added and the mixture was heated at 80° C. for 3 h. The mixture was poured onto ice cold 1N HCl (2 mL) and extracted with EtOAc (3×2 mL). The combined organic fractions were washed with water (2 mL) and then dried over Na2SO4. The solvent was evaporated. Purification by Combiflash chromatography (SiO2-12 g, gradient elution of 30-60% EtOAc/hexanes over 25 min) gave the title compound.

Workup

additionThe mixture was poured onto ice cold 1N HCl (2 mL)
extractionextracted with EtOAc (3×2 mL)
washThe combined organic fractions were washed with water (2 mL)
dry with materialdried over Na2SO4
customThe solvent was evaporated
customPurification
washby Combiflash chromatography (SiO2-12 g, gradient elution of 30-60% EtOAc/hexanes over 25 min)

Sources & evidence

ORD record: ord-cfe3ce53471e42a1aa3cc79513970229
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08063224B2

Reaction notes

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