1-Phenylcyclobutanecarbonitrile Chemical Properties

Boiling point:

85°C/0.3mmHg(lit.)

Density 

1.03

refractive index 

1.5313-1.5333

storage temp. 

Sealed in dry,Room Temperature

form 

Liquid

color 

Clear light yellow

NIST Chemistry Reference

Cyclobutanecarbonitrile, 1-phenyl-(14377-68-5)

Safety Information

Hazard Codes 

Xn

Risk Statements 

36/37/38-20/21/22

Safety Statements 

36/37/39-26

HS Code 

29269095

MSDS

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1-Phenylcyclobutanecarbonitrile Usage And Synthesis

Chemical Properties

CLEAR LIGHT YELLOW LIQUID

Uses

1-Phenylcyclobutanecarbonitrile is used as a reactant in the preparation of a novel diacylglycerol acyltransferase-1 (DGAT-1) inhibitor.

Synthesis

The general procedure for the synthesis of 1-phenylcyclobutanecarbonitrile from phenylacetonitrile and 1,3-dibromopropane was as follows: powdered potassium hydroxide (536 g, 9.56 mol, 5.6 eq.) was suspended in a solvent mixture of toluene (1.54 L) and water (154 mL) and heated to 45 °C. Subsequently, tetrabutylammonium bromide (28 g, 0.85 mol, 0.05 eq.) and 1,3-dibromopropane (379 g, 1.88 mol, 1.1 eq.) were added followed by the slow dropwise addition of a toluene (500 mL) solution of phenylacetonitrile (200 g, 1.7 mol, 1.0 eq.) over a period of 42 min. During the dropwise addition, the reaction temperature was raised to 95 °C and the mixture was heated to reflux after the dropwise addition was completed. The resulting pink slurry was stirred at reflux temperature for 1 h. The completion of the reaction was confirmed by HPLC analysis. The reaction mixture was cooled to 20-25 °C and filtered through a Celite pad. The solid residue was washed with toluene (1.0 L), and the combined filtrates were washed sequentially with water (2 × 300 mL) and brine (150 mL), dried over anhydrous magnesium sulfate and filtered, and concentrated to give the crude product 1-phenylcyclobutanecarbonitrile (263 g) as an orange oil. The crude product was purified by vacuum distillation (boiling point 105 °C/750 mT) to give 1-phenylcyclobutanecarbonitrile in colorless liquid form [140 g, yield 52%, purity 97.7% (AUC)]. The major impurity was identified as B2 (2.3% AUC) (see Example 9, Synthesis of B section for details).

References

[1] Tetrahedron Letters, 2006, vol. 47, # 23, p. 3871 - 3874
[2] Journal of Organometallic Chemistry, 1993, vol. 448, # 1-2, p. 9 - 14
[3] Journal of Medicinal Chemistry, 2015, vol. 58, # 18, p. 7341 - 7348
[4] Patent: US2015/266876, 2015, A1. Location in patent: Paragraph 0160; 0161
[5] Patent: US2015/57443, 2015, A1. Location in patent: Paragraph 0247; 0248

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