5-Oxo-L-proline 1,1-dimethylethyl ester

Aqueous perchloric acid (70percent, 5 mL) was added to a solution of (S)-5-oxopyrrolidine-2-carboxylic acid (20 g, 154.9 mmol) in tert-butyi acetate (260 mL) at ambient temperature. The mixture was stirred at ambient temperature for 18 hrs in a 500 mL round bottom flask sealed with a rubber septum and then poured carefully into sat. sodium bicarbonate (200 mL). The mixture was extracted with ethyl acetate (2x200 mL) and the combined extract was dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product solidified under high vacuum. The solid was treated with a 10:1 hexanes/diethyl ether mixture. The solids were collect by filtration and dried to give (S)-tert-buty{ 5-oxopyrrolidine-2-carboxylate (21.65 g, 116.9 mmol, 75.5percent), clean as a white solid.To a suspension of L-Pyroglutamic acid (6.46 g, 50.0 mmol) and tBuOAc (100 mL) in a pressure flask was added HCIO4 (70 percent, 1.51 mL 0.35 equiv.) and the solution was stirred for 24 h at room temperature. It was poured into a sat. aq. NaHCO3 solution(200 mL), the organic phase was separated and the aqueous phase was extracted with CH2CI2 (2 x 100 mL). The combined organic phases were dried over MgSO4, filtered and the solvent was evaporated under reduced pressure to afford the title compound (6.87 g, 37.1 mmol, 74 percent) as a colorless solid.Rf: 0.41 (EtOAc, KMnO4)1H-NMR (300 MHz, CDCI3): 6 = 1.44 (s, 9 H, 3 x CH3), 2.12—2.15 (m, 4 H, 2 x4.08—4.16 (m, 1 H, CH), 6.11 (Sbr, 1 H, NH).13C-NMR (75.5 MHz, CDCI3): 6 = 25.08, 28.18, 29.58, 56.25, 82.62, 171.2, 177.9.Example 5-3 To a suspension of L-Pyroglutamic acid (6.46 g, 50.0 mmol) and tBuOAc (100 mL) in a pressure flask was added HClO[0492] To a solution of L-pyroglutamic acid (5.0 g, 38.73 mmol) in tert-butyl acetate (65 mL, 0.48 mol) was added 70percent aqueous perchloric acid (1.25 mL). The reaction mixture was stirred in a 250 mL round-bottom flask under N2 protection for 18 h and then carefully poured into saturated aqueous sodium bicarbonate solution. The resulting mixture was extracted with ethyl acetate (200 mL x 2). The combined organic layers were dried over anhydrous Na2SO4, and then concentrated. The residue was precipitated from a mixture of hexanes/ether (10:1). The solid was collected by filtration, and then dried to give (S)-tert-butyl 5-oxopyrrolidine-2-carboxylate S2 as a white solid (5 g, yield 70percent).The synthesis of the vinylproline derivative 6a was conducted proceeding from L-pyroglutamic acid (1a) in six steps (scheme 3). As an alternative, the synthesis of 6a was developed in five stages proceeding from L-proline (16a) with the aid of an electrochemical oxidation of 17a as the key step (step p). As a further suitable intermediate, compound 6b was synthesized by Cu-catalyzed substitution of the methoxy group in 4a (scheme 3).To a suspension of S- (-)-pyroglutamic acid (12.9 g, 0.1 mol) in 200 ml of t-butyl acetate, 70percent perchloric acid (3 ml, 0.11 mol) was added and the reaction mixture was stirred overnight in a tightly closed flask. Then the reaction mixture was slowly poured into a saturated solution of NAHC03 and the product was extracted with ether. The organic phase was washed with brine, dried over magnesium sulfate and evaporated to dryness to provide 11.3 g (60percent yield) of t- butyl L-PYROGLUTAMATE. An analytical sample can be obtained by crystallization in ether-hexane, m. p. 91-92 XB0;C.To a 2L 3-neck round bottom flask equipped with overhead stirring, nitrogen inlet, and thermocouple was charged L-pyroglutamic acid (40 g., 310 mmol), DCM (400 mL), and H2SO4 (16.51 mL, 310 mmol) the resulting slurry was cooled to 0 70percent Perchloric acid (0.85 cmtert-Butyl (S)-5-oxo-2-pyrrolidinecarboxylate (1a) To a stirred suspension of isopropyl (+)-L-pyroglutamate (5g, 38 mmol), in AcOtBu (50 mL, 11 equiv.) was addeddeopewise 70percent aq. HClO4 (2.5 mL, 30 mmol) and the solution was left to react overnight at room temperature.Na2CO3 (2.53.3 g, 0.0250.033 mol) was then added portionwise followed by Et2O (50 mL). The organic phase waswashed with 1M aq. Na2CO3 (20 mL×2) and brine (20 mL×2), the aqueous phase was extracted with AcOEt (100 mL).The organic phases were dried over anhydrous MgSO4 and evaporated to give an oil which crystallized in Et2O ascolorless crystals and was collected in first crystallization 2.850 g in 40percent yield.Triethylamine (14.5 g, 0.143 mol) was added to a stirred suspension of l-pyroglutamic acid 5 (5.2 g, 0.040 mol) in propylene carbonate (40 mL). A stirred mixture of pyroglutamic acid 5 (5.0g, 38.7mmol), Boc anhydride (16.9g, 77.4mmol), and DMAP (0.2g, 1.6mmol) in tert-BuOH (20mL) was refluxed for 12h under nitrogen atmosphere. Upon cooling at room temperature, solvent was removed under vacuum, and the residue was purified by flash chromatography (SiO

Molecular Weight:185.22
XLogP3:0.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:185.10519334
Monoisotopic Mass:185.10519334
Topological Polar Surface Area:55.4
Heavy Atom Count:13
Complexity:230
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes