4-Benzyl-3-(3-methyl-butyryl)-oxazolidin-2-one Chemical Properties

Boiling point:

412.9±14.0 °C(Predicted)

Density 

1.152±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

pka

-2.33±0.40(Predicted)

Appearance

Off-white to light yellow Solid

optical activity

Consistent with structure

Safety Information

Risk Statements 

36-43

Safety Statements 

26-36/37/39

HS Code 

29349990

4-Benzyl-3-(3-methyl-butyryl)-oxazolidin-2-one Usage And Synthesis

Uses

(4S)-4-Benzyl-3-isovaleryloxazolidin-2-one is an intermediate in the preparation of orally active renin inhibitor Aliskiren (A536000).

Synthesis

The general procedure for the synthesis of 3-isovaleryl-4(R)-benzyl-2-oxazolidinones from (S)-4-benzyl-2-azolidinones and isovaleryl chloride is as follows: 1. 4-Dimethylaminopyridine (2.55 g, 21.3 mmol) and triethylamine (46.9 mL, 340.8 mmol) were dissolved in dry dichloromethane (100 mL) to prepare solution A. The solution was prepared as follows. 2. (S)-(-)-4-benzyl-2-oxazolidinone (37.7 g, 213 mmol) was prepared by dissolving (S)-(-)-4-benzyl-2-oxazolidinone (37.7 g, 213 mmol) in another dry dichloromethane (300 mL). 3. Solution A was slowly added to Solution B and stirred well. 4. A solution of isovaleryl chloride (33.75 mL, 207 mmol) in dichloromethane (50 mL) was added slowly dropwise to the above mixture at 0 °C, controlling the internal temperature to be below 10 °C. 5. The reaction mixture was stirred at 10 °C for 30 minutes and then filtered to remove the salt formed. 6. Water (100 mL) was added to the filtrate to separate the organic and aqueous phases. 7. The organic phase was washed sequentially with water (100 mL) and brine (100 mL) and then dried over anhydrous sodium sulfate. 8. The solvent was removed by pressurized evaporation to give 53 g of a yellow oil, which solidified gradually over time in 95% yield. The NMR data of the product were as follows: 1H NMR (300 MHz, CDCl3, 298K) δ 7.35-7.15 (m, 5H), 4.71-4.61 (m, 1H), 4.21-4.10 (m, 2H), 3.35-3.25 (dd, J = 13.2, 3.4 Hz, 1H), 2.85-2.72 (dd, J = 14.97, 6.8 Hz, 1H), 2.80-2.72 (dd, J = 14.97, 6.8 Hz, 1H), 2.80-2.80 (dd, J = 14.97, 6.8 Hz, 1H). 1H), 2.80-2.67 (m, 2H), 2.29-2.12 (sept, J = 13.2 Hz, 1H), 1.03-0.98 (d, J = 6.8 Hz, 3H), 0.98-0.95 (d, J = 6.8 Hz, 3H). 13C NMR (75 MHz, CDCl3, 298K) δ 175.6, 171.2, 154.4, 137.1, 130.5, 130.2, 126.0, 82.1, 66.1, 45.6, 42.6, 41.4, 44.0, 28.7, 27.3, 19.7.

References

[1] Helvetica Chimica Acta, 2012, vol. 95, # 10, p. 1937 - 1945,9
[2] Patent: WO2011/151442, 2011, A2. Location in patent: Page/Page column 24
[3] Patent: US2013/71899, 2013, A1. Location in patent: Paragraph 0124-0127
[4] Journal of Medicinal Chemistry, 2016, vol. 59, # 23, p. 10530 - 10548
[5] Organic Process Research and Development, 2015, vol. 19, # 6, p. 611 - 617

4-Benzyl-3-(3-methyl-butyryl)-oxazolidin-2-one(104266-90-2)Related Product Information

• Aliskiren
• 4-Bromo-1-methoxy-2-(3-methoxy-propoxy)-benzene
• Benzenepropanol, 4-methoxy-3-(3-methoxypropoxy)-b-(1-methylethyl)-, (bR)-
• Benzaldehyde, 4-methoxy-3-(3-methoxypropoxy)-
• 2-Cyano-2,2-diMethyl-acetaMide
• Aliskiren inter-11
• 4-Methoxy-3-(3-methoxypropoxy)benzenemethanol
• Benzene, 4-[(2R)-2-(chloromethyl)-3-methylbutyl]-1-methoxy-2-(3-methoxypropoxy)-
• (4S)-(+)-4-Benzyl-3-propionyl-2-oxazolidinone
• 4-Benzyl-3-(5-chloro-2-isopropyl-pent-4-enoyl)-oxazolidin-2-one
• (3S,4S)-4-BENZYL-3-(3-METHYLPENTANOYL)-OXAZOLIDIN-2-ONE
• (N-ACETYL)-(4R)-BENZYL-2-OXAZOLIDINONE
• 4-Benzyl-3-(3-methyl-butyryl)-oxazolidin-2-one