Chloroacetyl chloride → 8-Acetyl-5-(benzyloxy)-2H-benzo[b][1,4]oxazin-3(4H)-one

HRID 470985Notes

Reaction equation

Cl[CH2:2][C:3](Cl)=[O:4].[NH2:6][C:7]1[C:8]([OH:24])=[C:9]([C:21](=[O:23])[CH3:22])[CH:10]=[CH:11][C:12]=1[O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(=O)([O-])O.[Na+].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[C:21]([C:9]1[C:8]2[O:24][CH2:2][C:3](=[O:4])[NH:6][C:7]=2[C:12]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:11][CH:10]=1)(=[O:23])[CH3:22]

Participants

Conditions

Temperature: 100 °C

Procedure

2-Chloroacetyl chloride (1.8 mL) was added dropwise to a stirred mixture of 1-(3-amino-4-(benzyloxy)-2-hydroxyphenyl)ethanone (example 11, step c) (5.2 g) and sodium hydrogen carbonate (3.74 g) in DMF (30 mL) and then stirred for 2 h. Cesium carbonate (7.90 g) was added and the mixture heated at 100° C. for 20 h. The mixture was cooled to ambient temperature, quenched with water (500 mL), extracted with ethyl acetate (2×200 mL), washed with water (3×300 mL) and brine, dried over anhydrous sodium sulphate, filtered and evaporated under vacuum. The solid residue was treated with diethyl ether, filtered and dried to afford the subtitled compound as a beige solid. Yield 5.7 g.

Workup

temperatureThe mixture was cooled to ambient temperature
customquenched with water (500 mL)
extractionextracted with ethyl acetate (2×200 mL)
washwashed with water (3×300 mL) and brine
dry with materialdried over anhydrous sodium sulphate
filtrationfiltered
customevaporated under vacuum
additionThe solid residue was treated with diethyl ether
filtrationfiltered
customdried

Sources & evidence

ORD record: ord-2245209a3ae342e59b432295b548beae
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08629271B2

Reaction notes

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