3-(BENZYLOXY)CYCLOBUTANONE Chemical Properties

Boiling point:

285℃

Density 

1.11

refractive index 

1.5225

Flash point:

126℃

storage temp. 

Inert atmosphere,Store in freezer, under -20°C

form 

clear liquid

color 

Colorless to Yellow

InChI

InChI=1S/C11H12O2/c12-10-6-11(7-10)13-8-9-4-2-1-3-5-9/h1-5,11H,6-8H2

InChIKey

GPPSQLLIFNWNSB-UHFFFAOYSA-N

SMILES

C1(=O)CC(OCC2=CC=CC=C2)C1

Safety Information

WGK Germany 

WGK 3

HS Code 

2914500090

Storage Class

11 - Combustible Solids

Hazard Classifications

Acute Tox. 4 Oral
Eye Irrit. 2

3-(BENZYLOXY)CYCLOBUTANONE Usage And Synthesis

Uses

3-(Benzyloxy)cyclobutanone is used as a reactant for the synthesis of cyclobutyl derivatives of 2''-deoxyadenosine 5''-triphosphate as inhibitors of HIV-1 reverse transcriptase.

Synthesis

The general procedure for the synthesis of 3-(benzyloxy)-1-cyclobutanone from the compound (CAS: 917887-34-4) was as follows: 26.5 L of diethyl ether was added to a 30-35 L reactor and the reactor was water cooled at the beginning of the addition. 1.064 kg of compound (VII) was added to the reactor. 0.932 L of perchloric acid (60%) was pre-diluted with 0.664 L of water and added slowly to the reactor over 20-30 minutes at 10°C. After addition of the acid, cooling was stopped and the reaction was stirred vigorously overnight at about 20°C. The reaction was quenched by the addition of 900 g of NaHCO3 dissolved in 8 L of water until the pH was about 7. The aqueous phase was discarded and the reaction mixture was washed with an additional 7 L of water. The ether was removed under vacuum, 2 L of toluene was added, and the crude mixture was azeotropically dried. The crude product was diluted to about 2 L with toluene and loaded onto a silica gel pad. The pad was wet packed and pre-eluted with toluene. For the separation of 1.5 kg batches, a silica gel pad with a diameter of 40 cm and a height of 22 cm was used. After the crude product was applied to the pad, it was eluted with eluent in the following order: 3 x 10 L toluene; 9 x 10 L toluene: ethyl acetate (95:5). The product grades were collected and the solvent was evaporated under vacuum. High vacuum was required to remove the last 5% of toluene. Final isolation gave 533 g of product (yield = 77%).GC analysis showed 95% product purity. The 1H NMR (500 MHz, CDCl3) data for compound (VIII) were as follows: δH 7.40-7.29 (m, 5H), 4.53 (s, 2H), 4.38 (tt, J = 6.6, 4.7Hz, 1H), 3.3-3.1 (m, 4H).

References

[1] Patent: WO2013/11115, 2013, A1. Location in patent: Paragraph 00059-00061
[2] Bulletin of the Chemical Society of Japan, 1984, vol. 57, # 6, p. 1637 - 1642
[3] Patent: US2009/233903, 2009, A1. Location in patent: Page/Page column 58
[4] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 12, p. 4064 - 4067
[5] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 3, p. 643 - 652

3-(BENZYLOXY)CYCLOBUTANONE(30830-27-4)Related Product Information

• 4-BENZYLOXYPROPIOPHENONE
• 3-(BENZYLOXY)CYCLOBUTANONE
• Cyclobutanone