1-(ETHOXYCARBONYL)-4-PIPERIDINECARBOXYLIC ACID

Preparation of 1-(Ethoxycarbonyl) piperidine-4-Carboxylic AcidTo a solution of (154.8 gm) Sodium hydroxide in (750 ml) purified water, Isonipecotic acid(250gm) was added at 0-10°C, followed by the slow addition of ethyl chloroformate (231 ml) at 5-20°C. The reaction mixture was heated to 20-30°C and maintained for 3 hrs at the sametemperature. After completion of the reaction, the reaction mass was acidified to a pH 1-2 byaddition of hydrochloric acid. Then toluene (750 ml) was added to the reaction mass and stirred for15 minutes at 25-30 °C. The organic layer was separated and concentrated under vacuum at below70°C to obtain a residue. The resi4ue_was_mixed. with cyclohexane (1250 ml) at 60-70°C, thencooled to 25-30°C and maintain for I hour at the same temperature. The resulted contents werefiltered, and washed with cyclohexane (1250 ml) and dried at 50-55°C. Percentage Yield: 92percent— Preparation of 1-(Ethoxycarbonyl) piperidine-4-Carboxylic AcidTo a solution of (154.8 gm) Sodium hydroxide in (750 ml) purified water, Isonipecotic acid(250gm) was added at 0-10°C, followed by the slow addition of ethyl chloroformate (231 ml) at 5-20°C. The reaction mixture was heated to 20-30°C and maintained for 3 hrs at the sametemperature. After completion of the reaction, the reaction mass was acidified to a pH 1-2 byaddition of hydrochloric acid. Then toluene (750 ml) was added to the reaction mass and stirred for15 minutes at 25-30 °C. The organic layer was separated and concentrated under vacuum at below70°C to obtain a residue. The resi4ue_was_mixed. with cyclohexane (1250 ml) at 60-70°C, thencooled to 25-30°C and maintain for I hour at the same temperature. The resulted contents werefiltered, and washed with cyclohexane (1250 ml) and dried at 50-55°C. Percentage Yield: 92percent5.16 g (40 mmol) of the starting material 4-piperidinecarboxylic acid was added to a 100 ml round bottom flask, Na2CO3 5.04 g (48 mmol) and 40 mL of water was added. 5.13 g (48 mmol) was dissolved in 40 mL of tetrahydrofuran, added dropwise to a round bottom flask and stirred at room temperature for 2 h. The reaction was evaporated to remove tetrahydrofuran rotary end, was added 60mL of water, adjusted to pH 2 with 2MHCl, extracted with EA (30mL × 3), combined EA phases were dried over anhydrous MgSO4, filtered and rotary-dry products acquired Intermediate 1 as a white solid. Yield 91.9percent.

Molecular Weight:201.22
XLogP3:0.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:3
Exact Mass:201.10010796
Monoisotopic Mass:201.10010796
Topological Polar Surface Area:66.8
Heavy Atom Count:14
Complexity:221
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes