Diisopropylamine → HCID 67051839, compound

Temperature

-78 °C

To a solution of diisopropylamine (6.5 mL, 46.3 mmol) in THF (200 mL) at −78° C. was added butyllithium (17 mL of a 2.5 M solution in hexanes, 42.5 mmol) over 5 min. The solution of lithium diisopropylamide was stirred for 15 min at −78° C. A solution of (S)-4-benzyl-3-propionyl-2-oxazolidinone (9.0 g, 38.6 mmol) in THF (100 mL) was added to the lithium diisopropylamide by addition funnel over 26 min. The reaction temperature was kept below −70° C. during the course of the addition. After the addition, the mixture was stirred for a further 30 min at −78° C. Then phenylmethyl 3-oxoazetidine-1-carboxylate (9.5 g, 46.3 mmol) was added by addition funnel over 25 minutes as a solution in THF (100 mL). Again, the reaction mixture was kept below −70° C. during the reagent addition. After stirring for an additional 1 hour at −78° C., the reaction mixture was quenched with saturated ammonium chloride solution and was then allowed to warm to rt. Water was added to dissolve any precipitated ammonium chloride, and ethyl acetate was added. The layers were partitioned, and the aqueous phase was extracted twice with ethyl acetate. The combined organic extracts were washed with 5% aqueous sodium bicarbonate, dried over sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography (50% ethyl acetate: 50% hexanes) to provide phenylmethyl 3-hydroxy-3-{(1R)-1-methyl-2-oxo-2-[(4S)-2-oxo-4-(phenylmethyl)-1,3-oxazolidin-3-yl]ethyl}azetidine-1-carboxylate as a white crystalline solid (6.03 g, 13.8 mmol, 36% yield). 1H NMR (400 MHz, CDCl3) δ 7.37 (m, 8H), 7.20 (d, 2H), 5.12 (s, 2H), 4.66 (m, 1H), 4.27-4.20 (m, 2H), 4.10 (q, 1H), 4.03-3.93 (m, 3H), 3.28 (dd, 1H), 2.77 (dd, 1H), 1.29 (d, 3H).

1. additionThe reaction temperature was kept below −70° C. during the course of the addition
2. additionAfter the addition
3. additionAgain, the reaction mixture was kept below −70° C. during the reagent addition
4. stirringAfter stirring for an additional 1 hour at −78° C.
5. customthe reaction mixture was quenched with saturated ammonium chloride solution
6. temperatureto warm to rt
7. additionWater was added
8. dissolutionto dissolve any precipitated ammonium chloride, and ethyl acetate
9. additionwas added
10. customThe layers were partitioned
11. extractionthe aqueous phase was extracted twice with ethyl acetate
12. washThe combined organic extracts were washed with 5% aqueous sodium bicarbonate
13. dry with materialdried over sodium sulfate
14. filtrationfiltered
15. concentrationconcentrated
16. customThe residue was purified by column chromatography (50% ethyl acetate: 50% hexanes)

ORD record

ord-2e7f716fcca54507a048385d7549a801

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08362002B2