(E)-3-[3'-(4"-Fluorophenyl)-1'-(1"-methylethyl)-1H-indol-2"-yl]-2-propnal Chemical Properties

Melting point:

129.0 to 133.0 °C

Boiling point:

497.6±45.0 °C(Predicted)

Density 

1.10

storage temp. 

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

solubility 

DMSO (Slightly), Methanol (Slightly)

form 

powder to crystal

color 

Light orange to Yellow to Green

InChI

InChI=1S/C20H18FNO/c1-14(2)22-18-7-4-3-6-17(18)20(19(22)8-5-13-23)15-9-11-16(21)12-10-15/h3-14H,1-2H3/b8-5+

InChIKey

DVWHSTKQJBIYCK-VMPITWQZSA-N

SMILES

C(=O)/C=C/C1=C(C2=CC=C(F)C=C2)C2=C(N1C(C)C)C=CC=C2

CAS DataBase Reference

93957-50-7(CAS DataBase Reference)

Safety Information

RIDADR 

UN 3077 9/PG III

HS Code 

2933.99.8290

HazardClass 

9

PackingGroup 

III

(E)-3-[3'-(4"-Fluorophenyl)-1'-(1"-methylethyl)-1H-indol-2"-yl]-2-propnal Usage And Synthesis

Uses

(E)-3-(3-(4-Fluorophenyl)-1-isopropyl-1H-indol-2-yl)acrylaldehyde is an intermediate in the synthesis of Fluvastatin (F601250), a synthetic HMG-CoA reductase inhibitor. Antilipemic.

Synthesis

The general procedure for the synthesis of (E)-3-(3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl)acrolein from the compound (CAS:34900-01-1) and 1-isopropyl-3-(4-fluorophenyl)indole is as follows: 1. A suspension of 3-(4-fluorophenyl)-1-(1-methylethyl)-1H-indole (35.8 g) with phosphorus trichloride (31.4 g) in acetonitrile (35 ml) was cooled to 5 °C to prepare a crude acrolein solution. A 32.3 g solution of Example 3a in acetonitrile (40 ml) was added dropwise over 30 minutes. 2. the reaction mixture was gradually warmed to 60 °C and stirred at this temperature for 4 hours. 3. water (300 ml) was added and stirring was continued at 60 °C for 1 h. The solid formed was filtered through a Buchner funnel and washed with 75 ml of water. 4. The wet solid (49.7 g) was dissolved in toluene (250 ml), diatomaceous earth (1 g) and charcoal (0.5 g) were added and stirred for 30 minutes at room temperature. 5. After filtration of the solid, the solvent was removed by distillation under reduced pressure and the residue was dissolved in isopropanol (72 ml) at 75 °C. 6. The solution was cooled to 20 °C and stirred for 1 h at room temperature. 7. The precipitate was filtered through a Buchner funnel, washed twice with isopropanol (15 ml) and dried under vacuum at 60 °C. Finally 30.2 g (70% molar yield) of the target product was obtained. Example 4b 3-[3-(4-fluorophenyl)-1-(1-methylethyl)-1H-indol-2-yl]-2-propenal was synthesized as follows: 1. A solution was prepared by cooling a suspension of 3-[3-(4-fluorophenyl)-1-(1-methylethyl)-1H-indole (130.7 g) with phosphorus trichloride (114.6 g) in acetonitrile (128 ml) to 5 °C. 2. a solution of crude acrolein (116.9 g from Example 4a) in acetonitrile (145 ml) was added dropwise over 60 min. 3. the reaction mixture was gradually warmed to 60 °C and stirred at this temperature for 6 hours. 4. After addition of water (1100 ml) and continued stirring at 60 °C for 1 h, the solid formed was filtered through a Buchner funnel and washed with water (250 ml x 3). 5. The wet solid (131 g) was dissolved in toluene (1050 ml), diatomaceous earth (2.7 g) and charcoal (4 g) were added and stirred at room temperature for 30 min. 6. After filtration of the solid, the mixture was washed with water (500 ml x 2), the phases were separated and the organic solvent was removed by distillation under reduced pressure. 7. The residue was dissolved with isopropanol (260 ml) at 75 °C, the solution was cooled to 10 °C and stirred for 1 hour. 8. The precipitate was filtered through a Buchner funnel, washed with isopropanol (60 ml x 3) and dried under vacuum at 60 °C. A final 84.2 g (53% molar yield) of the target product was obtained.

References

[1] Patent: EP1477474, 2004, A1. Location in patent: Page column 5 - 6
[2] Journal of Organic Chemistry, 1992, vol. 57, # 11, p. 3250 - 3252
[3] RSC Advances, 2015, vol. 5, # 48, p. 38748 - 38759

(E)-3-[3'-(4"-Fluorophenyl)-1'-(1"-methylethyl)-1H-indol-2"-yl]-2-propnal(93957-50-7)Related Product Information

• (E)-3-(furan-2-yl)acrylic acid
• 3-(4-Fluorophenyl)-1-isopropyl-1H-indole
• Acrolein
• 1-ISOPROPYL-2-ACROLEIN-3-(4-FLUOROPHENYL)-INDOLE