2-(3-Methoxypropoxy)-4-((R)-2-(bromomethyl)-3-methylbutyl)-1-methoxybenzene Chemical Properties

Melting point:

52-53 °C

Boiling point:

398.8±32.0 °C(Predicted)

Density 

1.173

storage temp. 

under inert gas (nitrogen or Argon) at 2-8°C

solubility 

Dichloromethane, Ethyl Acetate,

form 

Solid

color 

White

CAS DataBase Reference

172900-69-5(CAS DataBase Reference)

2-(3-Methoxypropoxy)-4-((R)-2-(bromomethyl)-3-methylbutyl)-1-methoxybenzene Usage And Synthesis

Chemical Properties

White Solid

Uses

Intermediate in the preparation of Aliskiren.

Synthesis

Example 1 Synthesis of (R)-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutyl bromide: (R)-2-[4-methoxy-3-(3-methoxypropoxy)benzyl]-3-methylbutanol (14.82 g, 50 mmol) was dissolved in N,N-dimethylformamide (234 mL), and phosphorus tribromide ( 14.33 g, 50 mmol) and the reaction temperature was controlled at 20 °C. The reaction mixture was stirred at 20 °C for 8 hours. After the reaction was completed, it was cooled to room temperature and the reaction solution was slowly poured into water (702 mL) and extracted three times with hexane. The hexane layers were combined and washed twice each with saturated sodium bicarbonate solution and saturated sodium chloride solution in turn. The organic layer was dried with anhydrous sodium sulfate, filtered and the filtrate was concentrated to give 17 g of oily product. Methanol (51 mL) was added to the oily product and the product was crystallized at a controlled temperature of -10°C. The crystals were collected by filtration. The crystals were collected by filtration and dried under vacuum at room temperature to give 14.3 g of white solid in 79.6% yield, melting point 51-53 °C, chiral purity ≥99.9%.1H NMR (ppm, CDCl3): δ 6.72-6.81 (m, 3H), 4.11 (t, J = 6.4 Hz, 2H), 3.84 (s, 3H), 3.58 (t, J = 6.4 Hz, 2H), 3.42 (dd, J = 4.5, 10.2 Hz, 1H), 3.36 (s, 3H), 3.30 (dd, J = 4.5, 10.2 Hz, 1H), 2.77 (dd, J = 4.8, 13.8 Hz, 1H), 2.48 (dd, J = 4.8, 13.8 Hz, 1H), 2.11 (m, 2H ), 1.86 (m, 1H), 1.60 (m, 1H), 0.99 (m, 6H).

References

[1] Helvetica Chimica Acta, 2003, vol. 86, # 8, p. 2848 - 2870
[2] Tetrahedron Letters, 2005, vol. 46, # 37, p. 6337 - 6340
[3] Patent: US2013/231509, 2013, A1. Location in patent: Paragraph 0021-0022
[4] Patent: WO2011/148392, 2011, A1. Location in patent: Page/Page column 62
[5] Patent: WO2012/78147, 2012, A1. Location in patent: Page/Page column 19-20

2-(3-Methoxypropoxy)-4-((R)-2-(bromomethyl)-3-methylbutyl)-1-methoxybenzene(172900-69-5)Related Product Information

• Anisole
• p-Anisaldehyde
• 4-Methoxyphenol
• Guaiacol
• 4-Methoxybenzyl cyanide
• METHOXYTRIMETHYLSILANE
• (Trifluoromethoxy)benzene
• POLY(ETHYLENE GLYCOL) METHYL ETHER ACRYLATE
• 3-Amino-2,2-dimethylpropionamide
• Aliskiren inter-8
• Aliskiren inter-11
• 1-(((S)-2-(Bromomethyl)-3-methylbutoxy)methyl)benzene
• 4-Pentenamide, 5-chloro-N,N-dimethyl-2-(1-methylethyl)-, (2S,4E)-
• Benzene, 4-[(2R)-2-(chloromethyl)-3-methylbutyl]-1-methoxy-2-(3-methoxypropoxy)-
• 4-Pentenoic acid, 5-chloro-2-(1-methylethyl)-, (2S,4E)-
• Benzene
• Aliskiren inter-10
• Aliskiren inter-6