Methanol → (2R,3S,5R,6R)6-Amino-2-carbamoyloxymethyl-2-methylpenam-3-carboxylic Acid p-Nitrobenzyl Ester

A solution of (2R,3S,5R,6R) 2-(N-acetyl)carbamoyloxymethyl-2-methyl-6-phenoxyacetamidopenam-3-carboxylic acid p-nitrobenzyl ester (1.17 g, 2.0 mmol) in methylene chloride (10 ml) at -40° was charged with dimethylaniline (1.03 ml, 8.0 mmol) and phosphorous pentachloride (0.92 g, 4.4 mmol). The solution was stirred at -35° to -40° for 30 minutes and cold (~-35° ) methanol (4.1 ml, 100 mmol) was added dropwise. The pale green solution was stirred at -35° to -40° for 2 hours and then quenched into ice-water (10 ml). The pH was adjusted to 1.7 with conc. ammonia and the layers were separated. The aqueous was washed with CH2Cl2 (5 ml), combined with a water back-extract (5 ml), and stirred with CH2Cl2 (10 ml) during pH adjustment to 6.5 with ammonia. The organic phase was withdrawn, washed (5 ml, H2O), combined with a back-extract (CH2Cl2, 10 ml), dried (4A sieves), filtered, concentrated to 4 ml and diluted with heptane (10 ml). The suspension was concentrated to 8 ml and the liquids were decanted. The solids were treated with CH2Cl2 (4 ml) and heptane (10 ml) in the same fashion, and the product was washed with heptane and dried to an off-white solid (0.28 g) 34% nmr 100 MHz CDCl3 -D2O δ 8.24 (2, d, J=8.5 Hz, 1/2 pNB AB), 7.56 (2, d, J=8.5, pNB AB), 5.68 (1, brd J=4, C5 -H), 5.32 (2, s, benzyl CH2), 4.76 (1, s, C3 -H) 4.55 (HOD overlapping C6 -H d), 4.16 and 3.97 (2, ABq J=11.5 C2 -CH2 -O), 1.43 (3, s, C3 -CH3), with 2.36 ##STR79##

1. stirringThe pale green solution was stirred at -35° to -40° for 2 hours
2. customquenched into ice-water (10 ml)
3. customthe layers were separated
4. washThe aqueous was washed with CH2Cl2 (5 ml)
5. extractionback-extract (5 ml)
6. stirringstirred with CH2Cl2 (10 ml) during pH adjustment to 6.5 with ammonia
7. customThe organic phase was withdrawn
8. washwashed (5 ml, H2O)
9. extractiona back-extract (CH2Cl2, 10 ml)
10. dry with materialdried (4A sieves)
11. filtrationfiltered
12. concentrationconcentrated to 4 ml
13. additiondiluted with heptane (10 ml)
14. concentrationThe suspension was concentrated to 8 ml
15. customthe liquids were decanted
16. additionThe solids were treated with CH2Cl2 (4 ml) and heptane (10 ml) in the same fashion
17. washthe product was washed with heptane
18. dry with materialdried to an off-white solid (0.28 g) 34% nmr 100 MHz CDCl3 -D2O δ 8.24 (2, d, J=8.5 Hz, 1/2 pNB AB), 7.56 (2, d, J=8.5, pNB AB), 5.68 (1, brd J=4, C5 -H), 5.32 (2, s, benzyl CH2), 4.76 (1, s, C3 -H) 4.55 (HOD overlapping C6 -H d), 4.16 and 3.97 (2, ABq J=11.5 C2 -CH2 -O), 1.43 (3, s, C3 -CH3), with 2.36

ORD record

ord-f4b28ab94e4f455894403ae24a7e99e3

Source dataset

uspto-grants-1984_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04426520