4-Morpholinepropanoic acid, methyl ester → 3-Morpholino-N-(2-phenylbenzo[d]oxazol-5-yl)propanamide

HRID 1896748

Reaction equation

[C:1]1([C:7]2[O:8][C:9]3[CH:15]=[CH:14][C:13]([NH2:16])=[CH:12][C:10]=3[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[O:17]1[CH2:22][CH2:21][N:20]([CH2:23][CH2:24][C:25](OC)=[O:26])[CH2:19][CH2:18]1.C[Al](C)C.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1>[O:17]1[CH2:22][CH2:21][N:20]([CH2:23][CH2:24][C:25]([NH:16][C:13]2[CH:14]=[CH:15][C:9]3[O:8][C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)=[N:11][C:10]=3[CH:12]=2)=[O:26])[CH2:19][CH2:18]1

Participants

Conditions

Temperature: 160 °C

Procedure

To 2-phenylbenzo[d]oxazol-5-amine (75 mg, 0.36 mmol) and methyl 3-morpholinopropanoate (63 μL, 0.39 mmol) in toluene (2.5 mL) was added a 2M solution of trimethylaluminum in toluene (0.22 mL, 0.43 mmol). The resulting solution was heated twice for 5 min at 160° C. in the microwave. After cooling, sodium bicarbonate solution was added and the aqueous layer was extracted with ethyl acetate. The organic layer was then washed with brine and the combined organic layers were dried over anhydrous MgSO4. After evaporation, the impurities were removed by filtering through on a plug of silica eluting with ethyl acetate/hexanes 50:50 v/v and the desired product was obtained by elution with methanol to afford 17.5 mg (14%) of the title compound (LCMS RT=5.54 min, MH+ 352.0)

Workup

temperatureAfter cooling
extractionthe aqueous layer was extracted with ethyl acetate
washThe organic layer was then washed with brine
dry with materialthe combined organic layers were dried over anhydrous MgSO4
customAfter evaporation
customthe impurities were removed
filtrationby filtering through on a plug of silica eluting with ethyl acetate/hexanes 50:50 v/v

Sources & evidence

ORD record: ord-65df4c1dc796480bb495e12218559b3e
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08518980B2

Linked notes

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