SPIRO[INDOLINE-3,4'-PIPERIDIN]-2-ONE

SPIRO[INDOLINE-3,4'-PIPERIDIN]-2-ONE Property

Boiling point:

413.2±45.0 °C(Predicted)

Density 

1.23±0.1 g/cm3(Predicted)

storage temp. 

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

pka

13.94±0.20(Predicted)

Appearance

White to off-white Solid

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P321Specific treatment (see … on this label).

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P362Take off contaminated clothing and wash before reuse.

SPIRO[INDOLINE-3,4'-PIPERIDIN]-2-ONE Chemical Properties,Usage,Production

Synthesis

Method 1: Procedure for the synthesis of spiro[indolin-3,4'-piperidin]-2-one. Hydroxyindole (3.00 g, 22.5 mmol) was dissolved in tetrahydrofuran (20 mL) under argon protection, and a tetrahydrofuran solution (20 mL) with benzylbis(2-chloroethyl)amine (5.20 g, 22.5 mmol) was added sequentially to tetrahydrofuran (100 mL). Sodium hydride (1.60 g, 67.6 mmol) was added at room temperature and the mixture was stirred at the same temperature for 1 hour, then warmed up to 90 °C and continued stirring for 3 hours. After the reaction solution was cooled to room temperature, a tetrahydrofuran solution (10 mL) of sodium hydride (0.540 g, 22.5 mmol) was added and stirring was continued at 90 °C for 12 hours. After the reaction was completed, saturated aqueous ammonium chloride solution was added and stirred for 10 min at room temperature. The mixture was poured into a mixture of saturated aqueous sodium bicarbonate solution and brine and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: chloroform:methanol=20:1) to afford 1'-benzylspiro[indoline-3,4'-piperidin]-2-one (2.94 g, 44.6% yield) as a yellow amorphous solid.1H-NMR (400 MHz, CDCl3) δ: 1.78-1.93 (m, 2H), 1.95-2.06 (m, 2H), 2.65-2.06 (m, 2H). 2H), 2.65-2.77 (m, 2H), 2.87-3.00 (m, 2H), 3.69 (s, 2H), 6.90 (d, J=7.6Hz, 1H), 7.02 (t, J=7.6Hz, 1H), 7.20 (t, J=7.6Hz, 1H), 7.26 (t, J=6.2Hz, 1H), 7.34 (t, J=6.2Hz, 1H), 7.34 (t, J=7.6Hz, 1H). J=7.6 Hz, 2H), 7.40-7.41 (m, 3H), 8.72 (s, 1H). 1'-Benzylspiro[indoline-3,4'-piperidin]-2-one (300 mg, 1.03 mmol) was dissolved in methanol (5 mL) and 10% palladium carbon (30.0 mg) was added. The mixture was stirred at room temperature under hydrogen atmosphere for 15 hours. The reaction solution was filtered through diatomaceous earth and concentrated under reduced pressure to give spiro[indoline-3,4'-piperidin]-2-one (187 mg, 90.2% yield) as a colorless amorphous solid.1H-NMR (400 MHz, CDCl3) δ: 1.73-1.78 (m, 2H), 1.88-1.94 (m, 2H), 3.06-3.12 (m, 2H) , 3.35-3.41 (m, 2H), 6.92 (d, J=7.7Hz, 1H), 7.04 (t, J=7.7Hz, 1H), 7.22 (t, J=7.7Hz, 1H), 7.42 (d, J=7.7Hz, 1H), 8.70 (br, 1H).

References

[1] Patent: US2008/306102, 2008, A1. Location in patent: Page/Page column 12
[2] ACS Medicinal Chemistry Letters, 2018, vol. 9, # 2, p. 94 - 97
[3] Patent: WO2014/60411, 2014, A1. Location in patent: Page/Page column 36