Hydrochloric Acid → 6-[2-(4-Bromo-2-chloro-phenyl)-propionyl]-2,2,4-trimethyl-4H-benzo[1,4]oxazin-3-one

HRID 2386852Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:22])[C:9]([C:11]2[CH:12]=[CH:13][C:14]3[O:18][C:17](=[O:19])[N:16]([CH3:20])[C:15]=3[CH:21]=2)=[O:10])=[C:4]([Cl:23])[CH:3]=1.Cl.C([O-])(O)=O.[Na+].Br[C:31](C)([CH3:35])[C:32](Br)=O>[OH-].[Na+].O1CCOCC1.O.CCOC(C)=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:22])[C:9]([C:11]2[CH:12]=[CH:13][C:14]3[O:18][C:31]([CH3:35])([CH3:32])[C:17](=[O:19])[N:16]([CH3:20])[C:15]=3[CH:21]=2)=[O:10])=[C:4]([Cl:23])[CH:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 5-[2-(4-bromo-2-chloro-phenyl)-propionyl]-3-methyl-3H-benzooxazol-2-one (20 mg, Example 116 step 7) in 1N aqueous NaOH (1 ml) and dioxane (1 ml) was heated for 20 min at 100° C. in a microwave oven. Aqueous 1N HCl solution (1.2 ml) was added, followed by NaHCO3 (100 mg) and EtOAc (10 ml). Bromoisobutyryl bromide (20 mg) was added and the mixture was stirred for 1 h. Water (10 ml) was added and extracted with EtOAc. The combined organic layers were dried over Na2SO4 and then concentrated to an oil. The residue was dissolved in DMF (3 ml), and K2CO3 (100 mg) was added. The mixture was heated to 100° C. for 2 h. The mixture was purified by prep. HPLC (C18-column, solvent gradient 20-98% CH3CN in 0.1% HCOOH[aq]) to give the title compound (11 mg) as a light yellow oil. MS (m/e)=438.0 [M+H+].

Workup

extractionextracted with EtOAc
dry with materialThe combined organic layers were dried over Na2SO4
concentrationconcentrated to an oil
dissolutionThe residue was dissolved in DMF (3 ml)
additionK2CO3 (100 mg) was added
temperatureThe mixture was heated to 100° C. for 2 h
customThe mixture was purified by prep

Sources & evidence

ORD record: ord-c684deacf344417b9391f9dcd21b3b21
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08268820B2

Reaction notes

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