Chloral → HCID 13591263, compound

Temperature

-40 °C

7.7 g of molecular sieve 3 Å and, after a few minutes, 2.3 ml (23.5 mmols--4.7 equivalents) of anhydrous trichloroacetaldehyde were added to a solution of 1.35 g (5 mmols) of tert.-butyl (6R, 7R)-7-amino-3-methoxy-8-oxo-5-oxa-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate in 81 ml of benzene. The mixture was heated at the boiling point for 2.5 hours, with stirring, cooled, filtered rapidly and concentrated in vacuo. The residue was dissolved in 23 ml of anhydrous tetrahydrofuran and the solution was cooled to --40° C. 0.89 ml (5.1 mmols--1.02 equivalents) of ethyldiisopropylamine was added and the mixture was stirred at -40° C. and then allowed to warm to 0° C. At this temperature, a precooled solution of 2.18 mg of potassium borohydride in 35 ml of 50 percent strength aqueous tetrahydrofuran was added rapidly and the mixture was stirred for 5 minutes. The reaction was then quenched with a mixture of 38 ml of 2N HCl and 17 ml of acetonitrile at 0° C. and the mixture was subsequently stirred for a further 2 hours. For working up, the mixture was poured into saturated NaHCO3 solution and extracted with methylene chloride and the extract was washed with water and dried over MgSO4. After the solvent had been evaporated off in vacuo and the residue had been chromatographed on 120 g of silica gel (ethyl acetate:acetone 6:4), 372 mg (28%) of the title compound were obtained as a colorless rigid foam.

1. wait7.7 g of molecular sieve 3 Å and, after a few minutes
2. temperatureThe mixture was heated at the boiling point for 2.5 hours
3. temperaturecooled
4. filtrationfiltered rapidly
5. concentrationconcentrated in vacuo
6. dissolutionThe residue was dissolved in 23 ml of anhydrous tetrahydrofuran
7. addition0.89 ml (5.1 mmols--1.02 equivalents) of ethyldiisopropylamine was added
8. stirringthe mixture was stirred at -40° C.
9. temperatureto warm to 0° C
10. additionAt this temperature, a precooled solution of 2.18 mg of potassium borohydride in 35 ml of 50 percent strength aqueous tetrahydrofuran was added rapidly
11. stirringthe mixture was stirred for 5 minutes
12. customThe reaction was then quenched with a mixture of 38 ml of 2N HCl and 17 ml of acetonitrile at 0° C.
13. stirringthe mixture was subsequently stirred for a further 2 hours
14. additionthe mixture was poured into saturated NaHCO3 solution
15. extractionextracted with methylene chloride
16. washthe extract was washed with water
17. dry with materialdried over MgSO4
18. customAfter the solvent had been evaporated off in vacuo
19. customthe residue had been chromatographed on 120 g of silica gel (ethyl acetate:acetone 6:4)

ORD record

ord-37eeca2a5f4443c8b89398da644a24cd

Source dataset

uspto-grants-1986_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04616084