Hydrochloric Acid → 2-[4-[4-(2-Methyl-tetrazol-5-yl)-2,6-dimethylphenoxy]-1-hydroxy-butyl]-7-azaindole

温度

-50 °C

To a cold solution of 1-phenylsulfonyl-7-azaindole (1.29 g, 5 mmol) in 250 ml of THF was added at -30° C. n-BuLi (2.5M in hexane, 4 ml, 10 mmol). The mixture was stirred at -30°-40° C. for 1 h and then cooled to -50° C. To the above mixture was added dropwise at -50° C. a solution of 4-[4-(2-methyl-tetrazol-5-yl)-2,6-dimethylphenoxy]butyraldehyde (1.37 g, 5 mmol) in 25 ml of THF, and the mixture was stirred at -40°-50° C. for 1 h and then allowed to warm to -5° C. for 2 h. Water was added to the mixture, and the resulting reaction mixture was acidified with 1N HCl solution, and then re-basified with an aqueous sodium bicarbonate solution, extracted with methylene chloride, and the organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica column chromatography (20 cm column, ethyl acetate/hexane, 1/5-1/0; then methylene chloride/acetone 2/1-1/1) followed by recrystallization from methylene chloride/methanol to afford 501 mg (25%) of 2-[4-[4-(2-methyl-tetrazol-5-yl)-2,6-dimethylphenoxy]-1-hydroxy-butyl]-7-azaindole, as a white crystalline solid, m.p.166°-169° C.

1. stirringthe mixture was stirred at -40°-50° C. for 1 h
2. temperatureto warm to -5° C. for 2 h
3. customthe resulting reaction mixture
4. extractionre-basified with an aqueous sodium bicarbonate solution, extracted with methylene chloride
5. dry with materialthe organic layer was dried over sodium sulfate
6. concentrationconcentrated in vacuo
7. customThe residue was purified by silica column chromatography (20 cm column, ethyl acetate/hexane, 1/5-1/0
8. customthen methylene chloride/acetone 2/1-1/1) followed by recrystallization from methylene chloride/methanol

ORDレコード

ord-18d12d7ae0ef449493ec80a9679d7a04

出典データセット

uspto-grants-1997_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05618821