Tetrahydrofuran → 4-(2-((Tetrahydro-2H-pyran-2-yl)oxy)ethyl)benzaldehyde

Temperature

-78 °C

A mixture of 11.3 g of 4-(2-(2-tetrahydropyranyloxy)ethyl)-1-bromobenzene and 100 ml of tetrahydrofuran was cooled to −78° C., to which 25.9 ml of 1.56 M solution of n-butyl lithium in n-hexane was added dropwise over 15 minutes. After stirring at −78° C. for 1 hour, 4.2 ml of N,N-dimethylformamide was added dropwise at the same temperature over 15 minutes. After further stirring at −78° C. for 1 hour, 100 ml of saturated aqueous ammonium chloride solution was added, and the stirring was further continued until the reaction mixture came to room temperature. The reaction mixture was extracted twice with 200 ml of ethyl acetate, and the ethyl acetate layers were combined, washed three times with saturated aqueous ammonium chloride solution, and washed with saturated aqueous sodium chloride solution. The combined ethyl acetate layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give a residue. This residue was subjected to silica gel chromatography, which afforded 7.20 g (yield, 78%) of 4-(2-(2-tetrahydropyranyloxy)ethyl)-benzaldehyde, nD24.5 1.5311.

1. additionwas added dropwise over 15 minutes
2. stirringAfter further stirring at −78° C. for 1 hour
3. customcame to room temperature
4. extractionThe reaction mixture was extracted twice with 200 ml of ethyl acetate
5. washwashed three times with saturated aqueous ammonium chloride solution
6. washwashed with saturated aqueous sodium chloride solution
7. dry with materialThe combined ethyl acetate layer was dried over anhydrous magnesium sulfate
8. concentrationconcentrated under reduced pressure
9. customto give a residue

ORD record

ord-4654936b874347a29109aba9f10a8d68

Source dataset

uspto-grants-2002_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06437184B1