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 aldehyde 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 record

ord-0c98df28f3b549ccbd495c45dea16598

Source dataset

uspto-grants-2001_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06306895B1