Cesium carbonate → 2-(7-Methyl-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester

HRID 519220Notes

Reaction equation

[CH3:1][C:2]1[CH:12]=[CH:11][C:5]2[NH:6][C:7](=[O:10])[CH2:8][O:9][C:4]=2[CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH:20]([CH3:26])[C:21]([O:23][CH2:24][CH3:25])=[O:22]>CN(C=O)C>[CH2:24]([O:23][C:21](=[O:22])[CH:20]([N:6]1[C:5]2[CH:11]=[CH:12][C:2]([CH3:1])=[CH:3][C:4]=2[O:9][CH2:8][C:7]1=[O:10])[CH3:26])[CH3:25]

Participants

Conditions

Temperature: 70 °C

Procedure

To a mixture of 7-methyl-4H-benzo[1,4]oxazin-3-one (14.1 g, 86 mmol) and Cs2CO3 (70.4 g, 216 mmol) in DMF (500 mL) was added ethyl 2-bromopropanoate (31.3 g, 173 mmol) at ambient temperature and the reaction mixture was heated to 70° C. for 3 h. The reaction mixture was cooled to ambient temperature and the DMF was removed in vacuo. Water (500 mL) was added to the residue and the aqueous solution was extracted with EtOAc (3×150 mL). The combined organic phase was washed with brine (100 mL) and dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 10% EtOAc in petroleum ether) to give 2-(7-methyl-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester as brown solid (22.2 g, 98%). TLC (eluting with 20% EtOAc/heptane) Rf=0.3.

Workup

temperatureThe reaction mixture was cooled to ambient temperature
customthe DMF was removed in vacuo
additionWater (500 mL) was added to the residue
extractionthe aqueous solution was extracted with EtOAc (3×150 mL)
washThe combined organic phase was washed with brine (100 mL)
dry with materialdried over anhydrous Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by column chromatography on silica gel (eluting with 10% EtOAc in petroleum ether)

Sources & evidence

ORD record: ord-de9e237bd04b4aa1a63b238f443ce334
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09115151B2

Reaction notes

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