Water → HCID 53633087, compound

Temperature

-78 °C

Under stirring at -78° C., a solution of ethyl 5-methoxycarbonyl-3-methyl-2-pentenoate (3.0 g) in ether (30 ml) is added to a solution of LiAlH4 (1.0 g) in ether (50 ml). The mixture is further, stirred for 30 minutes, after which cold water and a saturated aqueous solution of sodium hydrogen carbonate are added followed by extraction with ethyl acetate. The extract is worked up in the conventional manner and the residue is purified by column chromatography on silica gel (100 g) with CCl4 -ethyl acetate (10:1) as the eluent. The above procedure provides a colorless oil of ethyl 6-hydroxy-3-methyl-2-hexenoate. This product (2.6 g) is mixed with 3,4-dihydro-α-pyran (5.2 g) and under ice-cooling, concentrated hydrochloric acid (0.04 ml) is added. The mixture is stirred for 3 hours, after which a saturated aqueous solution of sodium hydrogen carbonate is added followed by extraction with ethyl acetate. The extract is worked up in the conventional manner and the residue is purified by column chromatography on silica gel (100 g) with CCl4 -ethyl acetate (10:1) as the eluent. This procedure provides a colorless oil of ethyl 3-methyl-6-(α-tetrahydropyranyloxy)-2-hexenoate. A solution of this product (3.5 g) in ether (50 ml) is added to a solution of LiAlH4 (1.0 g) in ether (100 ml) at -78° C. with constant stirring. The mixture is further stirred at -20° C. for an hour, at the end of which time the excess LiAlH4 is decomposed with cold water. To this reaction mixture is added a saturated aqueous solution of sodium hydrogen carbonate followed by extraction with ethyl acetate. The extract is worked up in the conventional manner and the residue is purified by column chromatography on silica gel (70 g) with CCl4 -ethyl acetate (3:1) as the eluent. The above procedure provides a colorless oil of VII (R4 =H, n=O, m=2, R5 =THP). This product (1.9 g) and VI (R=H3C, X=Y=OH) (2.0 g) are dissolved in dioxane (30 ml), followed by addition of a mixture of BF3 -ether (10 ml) and dioxane (20 ml) at room temperature with stirring. The mixture is kept stirred for 2 hours, at the end of which time it is diluted with cold water and extracted with ethyl acetate. The extract is worked up in the conventional manner to recover IIIb (R=H3C, X=Y=OH, n=O, m=3).

1. stirringstirred for 30 minutes
2. extractionfollowed by extraction with ethyl acetate
3. customthe residue is purified by column chromatography on silica gel (100 g) with CCl4 -ethyl acetate (10:1) as the eluent

ORD record

ord-23cc505e89694947a3fe52d55d61a6dd

Source dataset

uspto-grants-1989_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04818441