BOC-4-ABZ-OH

Light brown powder

To a mixture of 4-aminobenzoic acid 1a (5.00g, 36.5mmol) in dioxane (70mL) and water (35mL) were added NaOH (1.46g, 36.5mmol) followed by di-tert-butyl dicarbonate (11.9g, 54.8mmol). The reaction mixture was stirred at room temperature for 24h. Solvent was removed by rotary evaporation, and 3N aqueous hydrochloric acid was added dropwise to the residue to adjust pH 3. A precipitate was obtained, collected, washed with water, and dried to provide 2a (8.28g, 96percent) as a solid.4-(tert-butoxycarbonylamino)benzoic acid 4-N-tert-Butoxycarbonylaminobenzoic Acid (7). To a solution of 4-aminobenzoic acid 6 (520 mg, 3.8 mmol) in dioxane/HMore specifically, Compound B-2 was obtained as follows. 4-amino benzoic acid (B-1) (2.00g, 14.6mmol) was dissolved in 140mL of methanol. Then, (Boc)iert-Butyl 4-(qumolin-8-ylcarbamoyl)phenylcarbamate (45); A solution of 4-aminobenzoic acid (1.0 g, 7.3 mmol) and triethylamine (3.0 mL, 21.8 mmol) in l, 4-dioxane HGeneral procedure: Amine (1 mmol) was added to a magnetically stirred solution of guanidine hydrochloride (15 molpercent) and di-tert-butyl dicarbonate (1.2 mmol) in EtOH (1 mL), at 35-40°C and stirred for appropriate time (Table 1). After completion of the reaction (followed by TLC or GC), EtOH was evaporated under vacuum and the residue either was washed with water to remove the catalyst or was dissolved in CHTriethylamine (0.4 ml, 3 mmol) followed by di-tert-butyldicarbonate (0.6 g, 3 mmol) is added to a mixture of 4-aminobenzoic acid (0.2 g, 1.5 mmol) in dioxane (4 ml) and HTo a stirred solution of 4-aminobenzoic acid 6a (5.00 g, 36.5 mmol) and sodium hydroxide (1.56 g, 39.3 mmol) in 1:1 water/dioxane (60 mL) at 0 °C was added di-tert-butyl dicarbonate (14.3 g, 65.4 mmol). The resulting mixture was stirred for 3 h, then warmed to room temperature and stirred overnight. The aqueous mixture was then washed with ethyl acetate (60 mL) before further ethyl acetate (60 mL) was added and the resulting mixture neutralised with 1 M aqueous KHSOGeneral procedure: Amine (1 mmol) and di-tert-butyl dicarbonate [(Boc)2O] (1.1 mmol) were placed in a microwave reaction vial. The LG microwave oven MG 555f was programmed to 300 W at 100 °C. The reaction was monitored using TLC. After the reaction, ice water was added to the reaction mixture which resulted in the precipitation of the product. The solid product was merely filtered off and washed with excess cold water. The product was pure enough for all practical purposes. For characterization purpose, it was further purified by column chromatography (Neutral Alumina as adsorbent, solvent system: Hexane: Ethyl acetate (7.5:2.5)).#10;General procedure: To a solution of 12a (2.0 g, 14.6 mmol) in 67percent 1.4-dioxane/water(48 mL) was added triethylamine (4.07 mL, 29.2 mmol) at room temperature and allowed to stir for 5 min. Di-tert-butyl decarbonate(6.37 mL, 29.2 mmol) was then added to the solution. After beingstirred for 26 h, the reaction mixture was concentrated and acidified with 2M hydrochronic acid to yield a white precipitate. The slurry wasthen filtered, washed with water and dried over in vacuo to afford 13a(2.94 g, 86percent) as a white solid.4-((tert-Butoxycarbonyl)amino)benzoic acid (13a). Yield: 86percent.1H NMR (300 MHz, CDCl3)δ 8.03 (2H, dt, J=8.8, 2.1 Hz), 7.46 (2H, dt, J=8.9, 2.0 Hz), 6.71 (1H, s, H-N), 1.54 (9H, s, tBu-O).Step-1: To a solution of 4-aminobenzoic acid (5.0 g, 36.44 mmol) in 1, 4-dioxan/10percent aq. NaHCOCommercially available 4-amino benzoic acid (5 g, 36 mmol) was dissolved in 1 M sodium hydroxide solution (40 mL, 40 mmol) and 1, 4 dioxane (30 mL). After the addition of di-tert-butyl dicarbonate (7.85 g, 36 mmol), the mixture was stirred at room temperature over the weekend. The dioxane was removed in vacuo and the residue was diluted with water (100 mL). Then concentrated hydrochloric acid (37percent) was added until pH3. The precipitate was collected by filtration, washed with water (100 mL) and air-dried to afford the title compound as a white solid (6.3 g, 72percent).To a solution of 4-aminobenzoic acid (ig, 7.29mmol) in a mixture of dioxane:water (2OmL:lOmL) was added sodium hydroxide (2M, 35mL). The mixture was stirred until complete dissolution and then it was added di-tert-butyl dicarbonate (3.18g, 14.S7mmol) at 0°C. The reaction mixture was stirred 24 hours at room temperature. The solvent was removed under reduced pressure and the crude was acidified with hydrogen chloride SN. The precipitate obtained was filtered and washed with water to obtain the title compound as a white solid (1 .23g, 71percent).LRMS (mlz): 238 (M+1)+STEP-5:Synthesis of compound 10A. N-BOC-4-aminobenzoic acid A mixture of compound 8 (300mg, 1.l3mmol) and NaOH (1M, 7mL) in MeOH (5 mL) was stirred at room temperature for overnight. After concentrated, the residue was dissolved in H20, 1 N HC1 was added until pH=2, and the mixture was extracted with EA. The organic layer was washed with brine, dried over Na2SO4 and concentrated to provide the product compound 9(200mg, yield: 74.5percent). It was used for the next step without further purification. ‘H NIVIR (DMSO-d6, 400MHz): 12.64 (s, 1H), 9.77 (s, 1H), 7.89(d, 2H, J = 8.4Hz), 7.61 (d, 2H, J = 8.8Hz), 1.54 (s, 9H).The ester prepared in preparation 24 (1.3 g, 4.90 mmol), lithium hydroxide (720 mg, 17.15 mmol), methanol (24.5 mL), water (24.5 mL), and tetrahydrofuran (73.5 mL), were combined in a 250 mL round bottomed flask, fitted with a stirbar, and under a nitrogen atmosphere. The mixture was stirred vigorously at room temperature for 16 hours, then concentrated under vacuum, dissolved in 1N HCl, and extracted with methylene chloride (100 mL*3). Organic layer was next dried (MgSO4), filtered, and concentrated under vacuum, yielding 1.07 g of white solid. This material was purified by silica gel chromatography, using a Chromatotron(R) with a 6000 uM rotor, in a 1:1 hexanes:ethyl acetate solvent system, yielding the title compound as 440 mg (38percent) white solid.[0181] Electrospray-MS 238.0 (M*+1).General procedure: A 20 ml vial equipped with a magnetic stirring bar was charged with secondary alcohols (0.3 mmol, 1 equiv.), NaN

Molecular Weight:237.25
XLogP3:2.7
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:4
Exact Mass:237.10010796
Monoisotopic Mass:237.10010796
Topological Polar Surface Area:75.6
Heavy Atom Count:17
Complexity:287
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes