BOC-GLY-PRO-OH

White to off-white powder

Then Boc-Gly-Pro-OMe was treated by NaOH aqueous solution and the free acid Boc-Gly-Pro-OH was given.General procedure: Dried THF:H2O (1:1) was added to Boc-gly-pro-OMe (2.86 g, 10 mmol)/Boc-Leu-pro-OMe (3.42 g, 10 mmol). To this, lithium hydroxide monohydrate (0.36 g, 15 mmol) was added at 0 C and stirred for 4-5 h. The product was isolated by adding water, acidifying upto pH 3 with KHSO4 and extracted with EtOAc (3 × 35 mL). The colorless oil was dried under reduced pressure and dried over NaSO4.(E) Synthesis of Boc-Gly-pro-OH Boc-Gly-Pro-OEt (4.11 g; 15.0 mmol) obtained in (D) was dissolved in MeOH (30 ml). The reaction was carried out for 1 hour after 2N-NaOH (10 ml) was added under ice cooling, and for 4 hours after the mixture was brought back to room temperature. The MeOH was distilled off under reduced pressure and the pH was adjusted to 2 with 1N-HCl The mixture was extracted three times with AcOEt. The extracts were washed with water and dried over anhydrous MgSO4, and the solvent was distilled off under reduced pressure. The residue was recrystallized from an AcOEt-n-hexane mixed solvent to give Boc-Gly-Pro-OH (3.44 g; 93%) as colorless plates. m.p. 140.5-141 C., specific rotation [alpha]D28 -75.5 (c=1.0, EtOH). TLC (developing solvent:1 CHCl3:MeOH:AcOH=80:10:5, 2 n-BuOH:AcOH:H2 O=4:1:1; color developing method:Boc-Gly-Pro-OH The Boc-Gly-Pro-OBz (19.4 g, 0.054 mol.) was dissolved in a mixture of 100 ml H2 O and 100 ml THF. After cooling the solution to 0 C., KOH (4.8 g, 0.085 mol.) in 50 ml H2 O was added slowly. The solution was stirred for one hour. Then, the THF was removed under reduced pressure and the aqueous solution was extracted with ethyl acetate to remove the benzyl alcohol. The resulting aqueous phase was covered by 200 ml ethyl acetate and was acidified at 0 C. to about pH 2 by addition of concentrated HCl slowly (vigorously swirling the solution at the same time). The product was extracted from the aqueous phase with ethyl acetate 3*200 ml. The organic layers were combined and washed with brine 2*30 ml, and dried by Na2 SO4. Removal of the ethyl acetate gave the product Boc-Gly-Pro-OH (white solid, 12.3 g, 85%) TLC Rf=0.25 (CMA, 85:15:3) FAB-MS, observed MH+ =273. 1 H-NMR (360 MHz, DMSO-d6, 20 C.) delta 12.55 (s, 1H, carboxyl), 6.79 (s, NH-major), 4.50 (dd, 0.25H, Pro alpha-minor), 4.20 (dd, 0.71H, Pro-alpha-major), 3.81-3.62 (m, 1.7H, Gly-alpha-major) 3.47-3.33 (m, 2H, Pro-delta and Gly-alpha-minor), 2.25-2.00 (m, 1.2H, Pro-beta), 1.96-1.60 (m, 2.7H, Pro-beta and Pro-gamma), 1.36 (s, 9H, Boc).A mixture of 3.5 g (0.02 m) of N-tert.butoxycarbonyl-glycerine, 5.4 g (0.04 m) of 1-hydroxybenzotriazole, 4.82 g (0.02 m) of proline, benzyl ester hydrochloride, 6 ml of N-ethylmorpholine and 50 ml of dry tetrahydrofuran was mixed with 4.12 g (0.02 m) of dicyclohexylcarbodiimide at 10 then was stirred for 1/2 hour in the cold and at room temperature for 17 hours. The mixture was filtered. The filtrate was evaporated and partitioned between ice water, dilute hydrochloric acid and ethyl acetate. The organic extract was washed with dilute hydrochloric acid, water, bicarbonate and brine. The dried extract was concentrated to leave 7.2 g of syrupy N-t-boc.-glycyl-L-proline, benzyl ester.A portion (10.3g= 0.05 mole) of dicyclohexylcarbodiimide (DCC) was added dropwise under stirring at 0 C. to a solution of General procedure: A mixture of compound 2a (2 mmol) and Pd/C (20 w%) in ethanol (30 mL) was hydrogenated for 3 hrs at atmospheric pressure.The reaction mixture was filtered off and concentrated in vacuo. The crude was taken in toluene and concentrated again, and then in Et2O/petroleum ether and concentrated once more to give compound 3a as a glassy solid in 62% yield overtwo steps. MS (ESI, EI-) m/z = 347 (MH-).

Molecular Weight:272.30
XLogP3:0.6
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:5
Exact Mass:272.13722174
Monoisotopic Mass:272.13722174
Topological Polar Surface Area:95.9
Heavy Atom Count:19
Complexity:375
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes