4-[2-(1-AZEPANYL)ETHOXY]BENZYL CHLORIDE HCL Chemical Properties

storage temp. 

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

Appearance

Off-white to gray Solid

Safety Information

HS Code 

29339900

4-[2-(1-AZEPANYL)ETHOXY]BENZYL CHLORIDE HCL Usage And Synthesis

Uses

1-[2-[4-(Chloromethyl)phenoxy]ethyl]hexahydro-1H-azepine Hydrochloride is a useful synthetic intermediate in the synthesis of Bazedoxifene (B129250); a nonsteroidal selective estrogen receptor modulator (SERM). Also used as an antiosteoporotic.

Synthesis

S4: (4-(2-(Azepan-1-yl)ethoxy)phenyl)methanol (561 g) obtained from step S3 was dissolved in 1.2 L of tetrahydrofuran and cooled to 0 °C. Thionyl chloride (320 g) was added slowly and dropwise under stirring, keeping the reaction temperature not exceeding 55 °C, and the reaction was gradually warmed up at this temperature for 6 hours. Upon completion of the reaction, about 600 mL of solvent was removed by distillation. To the residue was added 300 mL of ethyl acetate, the mixture was cooled to 0 °C and stirred for 30 minutes. It was subsequently filtered and the solid was washed with 300 mL of ethyl acetate. The resulting solid was dried to give 1-(2-(4-(chloromethyl)phenoxy)ethyl)azepane hydrochloride (619 g) in 90% yield and 99% HPLC purity.

References

[1] Patent: CN107400087, 2017, A. Location in patent: Paragraph 0045
[2] Patent: WO2011/22596, 2011, A2. Location in patent: Page/Page column 4; 24
[3] Patent: WO2011/22596, 2011, A2. Location in patent: Page/Page column 22; 23
[4] Angewandte Chemie - International Edition, 2013, vol. 52, # 22, p. 5795 - 5798
[5] Angew. Chem., 2013, p. 5999

4-[2-(1-AZEPANYL)ETHOXY]BENZYL CHLORIDE HCL(223251-25-0)Related Product Information

• 1-[4-(2-AZEPAN-1-YL-ETHOXY)-BENZYL]-5-BENZYLOXY-2-(4-BENZYLOXY-PHENYL)-3-METHYL-1H-INDOLE
• BAZEDOXIFENE ACETATE
• 3-METHYL-5-(PHENYLMETHOXY)-2-[4-(PHENYLMETHOXY)PHENYL]-1H-INDOLE
• BenzeneMethanol, 4-[2-(hexahydro-1H-azepin-1-yl)ethoxy]- (hydrochloride)
• Benzyl chloride