Oxalyl chloride → 6-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-7-methyl-3-(1,3-thiazol-2-yl)-1,2-benzoxazole-5-carbaldehyde

Oxalyl chloride (0.31 g, 2.4 mmol) was added to a stirred solution of 6-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-7-methyl-3-(1,3-thiazol-2-yl)-1,2-benzoxazole-5-carboxylic acid (Intermediate 326, 0.18 g, 0.4 mmol) and two drops DMF in dichloromethane (5 mL) at 0° C. and the mixture was stirred at room temperature for 2 hours. Solvent was removed under reduced pressure and the residue was dissolved in THF (10 mL) and the solution was cooled to −78° C. and 1M solution of lithium tri(t-butoxy)aluminum hydride (0.28 g, 1.1 mmol) was added slowly and it was stirred for 30 mins at the same temperature. The reaction was quenched with 1.5N hydrochloric acid and extracted with ethyl acetate, the combined organic layers were dried over sodium sulfate and the solvent was removed. The brown viscous oil thus obtained was purified by silica gel column chromatography (20% ethyl acetate in hexane) affording the product as yellow solid. Yield: 0.06 g (35%).

1. customSolvent was removed under reduced pressure
2. dissolutionthe residue was dissolved in THF (10 mL)
3. temperaturethe solution was cooled to −78° C.
4. stirringit was stirred for 30 mins at the same temperature
5. customThe reaction was quenched with 1.5N hydrochloric acid
6. extractionextracted with ethyl acetate
7. dry with materialthe combined organic layers were dried over sodium sulfate
8. customthe solvent was removed
9. customThe brown viscous oil thus obtained
10. customwas purified by silica gel column chromatography (20% ethyl acetate in hexane)

ORD-Eintrag

ord-e76c0023c6344a9fa73cd60e58539b19

Quelldatensatz

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08658641B2