8-acetyl-6-(benzyloxy)-2H-benzo[b][1,4]oxazin-3(4H)-one Chemical Properties

Boiling point:

517.2±50.0 °C(Predicted)

Density 

1.259±0.06 g/cm3(Predicted)

storage temp. 

Inert atmosphere,Room Temperature

solubility 

Chloroform, DCM, Methanol

pka

11.84±0.20(Predicted)

form 

Solid

color 

Beige

InChI

InChI=1S/C17H15NO4/c1-11(19)14-7-13(21-9-12-5-3-2-4-6-12)8-15-17(14)22-10-16(20)18-15/h2-8H,9-10H2,1H3,(H,18,20)

InChIKey

URTYAHMRXXVHKS-UHFFFAOYSA-N

SMILES

O1C2=C(C(C)=O)C=C(OCC3=CC=CC=C3)C=C2NC(=O)C1

Safety Information

HS Code 

2914390090

8-acetyl-6-(benzyloxy)-2H-benzo[b][1,4]oxazin-3(4H)-one Usage And Synthesis

Uses

8-Acetyl-6-benzyloxy-4H-benzo[1,4]oxazin-3-one is an intermediate in the synthesis of Olodaterol (O262000), a novel inhaled β2-adrenoceptor agonist with a 24h bronchodilatory efficacy.

Synthesis

The general procedure for the synthesis of 8-acetyl-6-(benzyloxy)-2H-benzo[b][1,4]oxazin-3(4H)-ones from 1-(3-amino-5-(benzyloxy)-2-hydroxyphenyl)ethanone and chloroacetyl chloride is as follows: 21.0 mL (258 mmol) of chloroacetyl chloride was slowly added dropwise under ice-bath cooling to a mixture containing 60.0 g (233 mmol) 1-(3-amino-5-benzyloxy-2-hydroxyphenyl)ethanone and 70.0 g (506 mmol) potassium carbonate. After dropwise addition, the reaction mixture was stirred at room temperature overnight, followed by heating to reflux temperature and continued stirring for 6 hours. Upon completion of the reaction, the reaction mixture was filtered while hot and the filtrate was concentrated to about 400 mL. ice water was added to the concentrate and a precipitate was precipitated. The precipitate was collected by filtration, dried and purified by chromatography using a short silica gel column (eluent ratio of dichloromethane:methanol = 99:1). The fractions containing the target product were combined, the solvent was evaporated and the residue was suspended in a mixed solvent of isopropanol/diisopropyl ether, diafiltered and washed with diisopropyl ether to give the pure product. Yield: 34.6 g (50% yield); MS data: [M + H]+ = 298.

References

[1] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 4, p. 1410 - 1414
[2] Patent: US2005/267106, 2005, A1. Location in patent: Page/Page column 7
[3] Patent: WO2005/111005, 2005, A1. Location in patent: Page/Page column 16
[4] Patent: US2007/249595, 2007, A1. Location in patent: Page/Page column 11
[5] Patent: US2007/88160, 2007, A1. Location in patent: Page/Page column 11

8-acetyl-6-(benzyloxy)-2H-benzo[b][1,4]oxazin-3(4H)-one(869478-09-1)Related Product Information

• 4-BENZYLOXYPROPIOPHENONE
• (R)-6-Benzyloxy-8-(oxiran-2-yl)-4H-benzo[1,4]oxazin-3-one
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• (R)-tert-butyl (4-cyano-2,3-dihydro-1H-inden-1-yl)carbamate
• 1-(5-(benzyloxy)-2-hydroxy-3-nitrophenyl)ethanone