Triethylamine → HCID 12069485, compound

Temperature

-78 °C

A solution of 3-cyclopentyl-2-(3,4-dichloro-phenyl)-propionic acid (prepared in Example 38, 5.00 g, 17.4 mmol) in tetrahydrofuran (150 mL) cooled to −78° C. was treated with triethylamine (2.77 mL, 19.9 mmol) followed by trimethylacetyl chloride (2.24 mL, 18.2 mmol). The resulting white slurry was stirred at −78° C. for 15 min and then at 0° C. for 45 min. In a separate flask, a solution of (S)-4-isopropyl-2-oxazolidinone (2.14 g, 16.57 mmol) in tetrahydrofuran (80 mL) cooled to −78° C. was treated with a 2.0M solution of n-butyllithium in hexanes (8.7 mL, 17.4 mmol). The solution was stirred at −78° C. for 10 min and then allowed to warm to 25° C. where it was stirred for an additional 10 min. At this time, the first reaction mixture was recooled to −78° C. The second reaction mixture was added to the first reaction mixture over a period of 5 min via cannula. The combined reaction was then stirred at −78° C. for 15 min and then allowed to warm to 25° C. where it was stirred for an additional 1.5 h. At this time, the reaction was quenched by the addition of a saturated aqueous sodium bisulfite solution (50 mL) and extracted with ethyl acetate (3×40 mL). The combined organic layers were washed with a saturated aqueous sodium bicarbonate solution (1×20 mL) and a saturated aqueous sodium chloride solution (1×20 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 85/15 hexanes/ethyl acetate) afforded (1) 3-[3-cyclopentyl-2(S)-(3,4-dichloro-phenyl)-propionyl]-4(S)-isopropyl-oxazolidin-2-one (2.15 g, 33%) as a clear oil: [α]23589=+87.5° (c=0.160, chloroform); EI-HRMS m/e calcd for C20H25Cl2NO3 (M+) 397.1211, found 397.1215 and (2) 3-[3-cyclopentyl-2(R)-(3,4-dichloro-phenyl)-propionyl]-4(S)-isopropyl-oxazolidin-2-one (1.88 g, 28%) as a white solid: mp 71.9-74.6° C.; [α]23589=−27.6° (c=0.188, chloroform); EI-HRMS m/e calcd for C20H25Cl2NO3 (M+) 397.1211, found 397.1212.

1. waitat 0° C. for 45 min
2. stirringThe solution was stirred at −78° C. for 10 min
3. temperatureto warm to 25° C. where it
4. stirringwas stirred for an additional 10 min
5. customwas recooled to −78° C
6. customThe second reaction mixture
7. additionwas added to the first reaction mixture over a period of 5 min via cannula
8. customThe combined reaction
9. stirringwas then stirred at −78° C. for 15 min
10. temperatureto warm to 25° C. where it
11. stirringwas stirred for an additional 1.5 h
12. customAt this time, the reaction was quenched by the addition of a saturated aqueous sodium bisulfite solution (50 mL)
13. extractionextracted with ethyl acetate (3×40 mL)
14. washThe combined organic layers were washed with a saturated aqueous sodium bicarbonate solution (1×20 mL)
15. dry with materiala saturated aqueous sodium chloride solution (1×20 mL), dried over sodium sulfate
16. filtrationfiltered
17. concentrationconcentrated in vacuo

ORD record

ord-f28ca98e8e27447cae72ba4f4409fea8

Source dataset

uspto-grants-2001_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06320050B1