Hydrochloric Acid → (2RS,6S)-6-(4-fluorophenoxymethyl)-2-methoxytetrahydropyran

To a solution of (2S)-1-(4-fluorophenoxy)-2-(methoxyethoxymethyloxy)-hexan-6-ol (1.25 g, 3.9 mmol) and oxalyl chloride (0.7 ml, 7.9 mmol) in dry CH2Cl2 was added dry DMSO (1.12 ml, 15.8 mmol) slowly at −78° C. The stirring was continued for a further 30 min. at −78° C. and quenched with dry Et3N (3.15 ml, 23.7 mmol). The reaction mixture was extracted with CH2Cl2 and dried (Na2SO4) to afford the crude aldehyde (1.1 g, 85%). A 20% methanolic HCl solution was added to the aldehyd and stirred for 5 h. at room temperature. The reaction mixture was neutralised with aqueous NaHCO3, extracted with ethyl acetate, dried (Na2SO4) and concentrated under vacuum. The crude product was purified by silica gel column chromatography to give a cis-trans mixture (2RS, 6S)-6-(4-fluorophenoxymethyl)-2-methoxytetrahydropyran (0.6 g, 80%) as a yellow syrup. TLC:ethyl acetate-light petroleum (1:3), Rf=0.8. 1H NMR (CDCl3, 200 MHz): δ 1.6-2.0 (m, 6H), 3.45 (s, 3H), 3.9-3.96 (m, 2H), 4.0-4.15(m, 1H), 4.8 (s, 1H), 6.8-7.01 (m, 4H).

1. extractionThe reaction mixture was extracted with CH2Cl2
2. dry with materialdried (Na2SO4)
3. customto afford the crude aldehyde (1.1 g, 85%)
4. extractionextracted with ethyl acetate
5. dry with materialdried (Na2SO4)
6. concentrationconcentrated under vacuum
7. customThe crude product was purified by silica gel column chromatography

ORD 기록

ord-76bff47c5c7a4b779fa03d41263ea2cf

출처 데이터셋

uspto-grants-2002_08

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US06433197B1