N-methyl-2-pyrrolidone → HCID 54064258, compound

A flask was charged with 60 mL THF, N-((R)-2-cyclobutyl)propionyl-(R)-4-benzyloxazolidinone (7.5 grams, 26.1 mmol, from Step C), and 32 mL water. The solution was cooled to 0 C and hydrogen peroxide (11.7 mL, 30%, 104 mmol) was added. Lithium hydroxide (1.25 grams, 52.2 mmol) was added and the mixture was stirred for 6 h at room temperature. The reaction was quenched with aqueous sodium sulfite and partitioned between water and methylene chloride. Sodium bicarbonate was added and the layers were separated. The aqueous layer was acidified with 2 N HCl and extracted with ether. The ether layers were combined and dried over sodium sulfate then concentrated to give 2.9 grams (87%) of the desired acid. The acid (2.9 grams, 18.7 mmol) was dissolved in 25 mL NMP and HBTU (17.7 grams, 46.8 mmol), HOBt (9.5 grams, 70.1 mmol) and diisopropylethylamine (16.3 mL, 93.5 mmol) was added. N-O-dimethylhydroxylamine hydrochloride (3.65 grams, 37.4 mmol) was added and the mixture was stirred for 5 h. The mixture was then diluted with ether and washed with water and sat'd NaCl. The ether was removed to give a precipitate which was filtered off and washed with 1/1 ether/pentane. The ether/pentane washes were combined and concentrated. Flash chromatography (1/1 pentane/ether) afforded 2.62 grams (71%) of the desired amide. 1H NMR (400 MHz, CDCl3). δ 1.05 (d, 3H), 1.62-1.93 (m, 4H), 1.98-2.12 (m, 2H), 2.5-2.3 (m, 1H), 3.18 (s, 3H), 3.72 (s, 3H).

1. washwashed with water
2. customThe ether was removed
3. customto give a precipitate which
4. filtrationwas filtered off
5. washwashed with 1/1 ether/pentane
6. concentrationconcentrated

ORD record

ord-2a0b4cb1db274112984a0ca960b6345e

Source dataset

uspto-grants-2001_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06265434B1