L-Pyroglutamic acid ethyl ester

White to cream low melting solid

A suspension of 30.0 g of L-pyroglutamic acid 133 (232 mmol) in 100 ml of anhydrous ethanol was slowly added with 20 ml of SOClThe synthesis of compound II specific process: To the reaction flask was added Compound I (10mmol), which was dissolved in absolute ethanol (15ml), cooled to -5 ~ 0 ° C, Thionyl chloride (11 mmol) in ethanol (10 ml) was slowly added dropwise to the system, Dropping is completed, slowly rose to room temperature reaction 10h. TLC point plate, the raw material completely reacted.The reaction mixture was evaporated to dryness under reduced pressure. The residue was dissolved in dichloromethane (50 ml) and water (50 ml), the layers were separated and the aqueous phase was extracted with dichloromethane (20 ml * 3). The organic phases were combined, The organic phase was dried over anhydrous sodium sulfate, filtered with suction and the filtrate was concentrated under reduced pressure to give compound II (9.8 mmo 1) in 98percent yield.General procedure: To a solution of L-pyroglutamic acid (10 mmol) in anhydrous alcohol(30 mL) was added catalytic amount of SOCl2 (1 mmol). The reaction mixture was stirred at room temperature for 12 h until no change was observed by TLC. After evaporating the solvent under reduced pressure, the residue was dissolved in EtOAc (100 mL), stirred over K2CO3, and dried with MgSO4 to afford the crude product. Then the residue passed through a flash column chromatography (MeOH/CH2Cl2=1/10) on silica gel and removal of all volatiles were in vacuo to give the pure products.A reaction vessel was charged with ethanol (49.0 liters) and cooled to -5°C. The reaction vessel was thencharged with thionyl chloride (4.97 kg) in a manner so that the temperature of the mixture did not exceed 0°C. Aftercomplete addition of the thionyl chloride, the mixture was cooled again to -5°C and L-pyroglutamic acid (Formula E) wasadded portionwise so that the temperature was maintained between 0 and -5°C during the addition. Following additionof the acid, the reaction mixture was heated to 20 to 25°C and stirred for 5 hours. The reaction mixture was thenevaporated under vacuum (T max 45°C) to approximately 15percent of its original volume. The remaining oil was then dissolvedin toluene (49 liters). The toluene solution was then cooled to approximately 10°C and triethyl amine (8.45 kg) was addedslowly so that the maximum temperature was between 20 and 25°C. The resulting suspension was stirred for 30 minutesand then filtered. The filter cake was washed with toluene (about 5 liters). The filtrate was reduced at 50°C under vacuumto a total volume of about 10 liters. Crystallization was initiated by slow addition of cyclohexane (8 liters) at 50°C andsubsequent cooling to approximately 30°C. After seed formation the mixture was cooled to 20 to 25°C and charged witha second 8 liter portion of cyclohexane. The mixture was then cooled to 6 to 8°C, stirred for one hour, and the resultingcrystals were filtered off. The crystals were washed twice with cyclohexane (4 liters each wash). The yield was 4.89 kg(82percent) L-pyroglutamic acid ethyl ester (Formula F) as colorless needles.To a solution of L-pyroglutamic acid 1 (13 g, 100 mmol) in anhydrous ethanol (50 mL) was slowly added SOCl2 (16.7 g, 130 mmol at 0°C, and the reaction mixture was stirred at this temperature for additional 3 h. The crude mixture was concentrated to dryness, the residue was dissolved in DCM (300 mL). The organic layer was washed brine and dried over anhydrous Na2SC>4, filtered and concentrated to dryness to give title compound 76, (S)-ethyl 5-oxopyrrolidine-2-carboxylate (13 g, 82percent yield). (LC method 1): m/z 158 (M+l)Thionyl chloride (1 1.2 mL, 154 mmol) was added to a solution of acid (20.0 g, 155.0 mmol) in ethanol (200 mL) at 0 °C slowly. The reaction mixture was allowed to stir at room temperature overnight. The mixture was concentrated in vacuo to remove ethanol. The crude residue was diluted with DCM, washed with saturated aqueous NaHC0To a solution of compound 18-1 (10.0 g, 77.5 mmol) in ethanol (150 mL) was added SOClTo a solution of compound 18-1 (10.0 g, 77.5 mmol) in ethanol (150 mL) was added SOCl2 (9.22 g, 77.5 mmol)dropwise at 0 °C. The mixture was stirred at 0 °C for 0.5 hour and at rt for another 3 hours. The reaction was monitoredby TLC and the mixture was concentrated in vacuo after the process stopped. The residue was purified by silica gelcolumn chromatography (EtOAc/MeOH (v/v) = 15/1) to give the title compound 18-2 as oil (8.5 g, 70percent). The compoundwas characterized by the following spectroscopic data:1H NMR (400 MHz, CDCl3): δ 7.04 (br, 1H), 4.10-4.22 (m, 3H), 2.22-2.48 (m, 3H), 2.07-2.22 (m, 1H), 1.22 (t, J = 7.1 Hz, 3H).

Molecular Weight:157.17
XLogP3:-0.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:157.07389321
Monoisotopic Mass:157.07389321
Topological Polar Surface Area:55.4
Heavy Atom Count:11
Complexity:179
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes