Diisopropylamine → HCID 86747096, compound

Temperature

-78 °C

To tetrahydrofuran (80 mL) is added n butyl lithium (15.5 mmol in hexane) and at -78° C. under argon is then added diisopropylamine (2.4 mL, 17.1 mmol). Methyl propanoate (15.3 mmol) is added neat over 5-6 minutes, and the mixture was stirred an additional 30 minutes at -78° C. A solution of 2-n-butyl-1-(2-chlorophenyl)methyl-4-(t-butyldimethylsilyloxy)methyl-1H-imidazol-5-carboxaldehyde (10.2 mmol) in tetrahydrofuran (10 mL) is added via a cannula, and the reaction mixture is stirred for 15 minutes. The reaction is partitioned between saturated ammonium chloride and ether, and the ether layer is washed with water, dried and concentrated to give crude product. This is chromatographed over silica gel with 20-50% of ethyl acetate in hexane to afford a mixture of isomeric β-hydroxyester products. A solution of this mixture (8.54 mmol) in methylene dichloride (100 mL) is treated with 4 dimethylaminopyridine (3 mmol) followed by acetic anhydride (84 mmol), and the solution is stirred at room temperature for 5 hours. The reaction is poured into water, stirred for 20 minutes and the product is extracted into ether. The ether extracts are washed with dilute hydrochloric acid solution, water, sodium bicarbonate solution and brine. The dried, concentrated mixture of β-acetoxyester products is used directly in the elimination reaction. To a solution of the β-acetoxyester product (4.5 mmol) in toluene (60 mL) is added of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (10.9 mmol), and the mixture is heated at 90° C. for 24 hours. The reaction is concentrated to 10 mL, diluted with ether and flash filtered through a 14×3 cm plug of silica gel with ether rinses to afford the crude olefinic product. Chromatography over silica gel with an ethyl acetate in hexane gradient gives homogeneous methyl (E) 3-[2-n-butyl-1-{(2-chlorophenyl)methyl}-4-(t-butyldimethylsilyloxy)methyl-1H-imidazol-5-yl]-2-propenoate. The elimination of the acetate with DBU produces predominantly the trans (E) isomer.

1. customat -78° C.
2. stirringthe reaction mixture is stirred for 15 minutes
3. customThe reaction is partitioned between saturated ammonium chloride and ether
4. washthe ether layer is washed with water
5. customdried
6. concentrationconcentrated
7. customto give crude product
8. customThis is chromatographed over silica gel with 20-50% of ethyl acetate in hexane
9. customto afford
10. stirringthe solution is stirred at room temperature for 5 hours
11. stirringstirred for 20 minutes
12. extractionthe product is extracted into ether
13. washThe ether extracts are washed with dilute hydrochloric acid solution, water, sodium bicarbonate solution and brine
14. concentrationThe dried, concentrated
15. additionmixture of β-acetoxyester products
16. customis used directly in the elimination reaction
17. temperaturethe mixture is heated at 90° C. for 24 hours
18. concentrationThe reaction is concentrated to 10 mL
19. additiondiluted with ether and flash
20. filtrationfiltered through a 14×3 cm plug of silica gel with ether rinses
21. customto afford the crude olefinic product

ORD record

ord-5baa1e57868946899d20cee179ea063c

Source dataset

uspto-grants-1993_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05234917