N-(Benzyloxycarbonyl)-6-aminohexanoic acid

White Solid

To a stirred suspension of 8-aminocaproic acid (1 g, 7.62 mmol) and K2CO3 (2.1 g, 15.2 mmol) inTHF (20 mL), benzyl-chloroformate (1.63 ml, 11.45 mmol) was added slowly. The mixture wasstirred at room temperature for 16 h. The reaction was quenched with AcOEt and H2O. Aqueousphase was separated and the pH of aqueous phase was adjusted to 2 by addition of HCl 4N andextracted twice with AcOEt (10 mL). Combined organic phases were then dried over anhydrousNa2SO4, filtered and evaporated in vacuum. The product 18 was used in the next step without anyfurther purification. Yield 99percent.To a stirred suspension of finely powdered 6-aminocaproic acid (32.79 g, 0.25 mol) in dichloromethane (500 ml), triethylamine (63.24 g, 0.625 mol) was added. Then, trimethylchlorosilane (54.32 g, 0.5 mol) was added dropwise with vigorous stirring and the resulting mixture was refluxed for 2 h. The reaction mixture was then cooled on an ice bath and benzyl chloroformate (95percent, 53.31 g, 0.313 mol) was added. The resulting mixture was stirred on ice for 60 min and at room temperature for 4 h. After removal of the solvent, the residue was distributed between 1000 ml of 4percent (v/w) solution of sodium hydrogen carbonate and 500 ml of methyl tert-butyl ether. The aqueous layer was separated, acidified to pH 2.0 with 2N hydrochloric acid and extracted three times with ethyl acetate. The combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated to yield clear oil (62.4 g, 94.1 percent) corresponding to target carboxylic acid 3* that was homogeneous by LC/MS and TLC, and was used in the next step with no further purification. MS m/z 265.33 (M+1)To a solution of 6-aminocaproic acid (1.0 g, 7.6 minol) and sodium hydroxide (0.6 g, 15.2 minol) in water (5 mL) at 0 °C was added dropwise a solution of benzyl chloroformate (1.6 g, 9.2 minol) in tetrahydrofuran (4 mL), and the mixture stirred at 0 °C for 30 min, thenroom temperature for 5 h. The mixture was then concentrated by half in vacuo, acidified to pH 3 with aqueous citric acid (1 M), extracted with dichloromethane (3 x), the combined organic layers dried over anhydrous magnesium sulfate and solution concentrated in vacuo to afford the title compound 74 (1.8 g, 89percent) as a white solid, which was used without further purification. m.p. 47-50 °C (Lit 56 oc34). 1H NMR (400 MHz, CDCI3) ö 1.33-1.40 (2H, m, H-4), 1.48-1.55 (2H, m, H-5), 1.61-1.68 (2H, m, H-3), 2.34 (2H, t, J = 7.3 Hz, H-2), 3.17-3.22 (2H, m, H-6), 4.80-4.84 (1H, m, NH), 5.09 (2H, s, CH2Ph), 7.26-7.38 (5H, m, Ph); 13C NMR (100 MHz, CDCI3) ö 24.3 (CH2, C-4), 26.1 (CH2, C-3), 29.6 (CH2, C-5), 33.8(CH2, C-2), 40.8 (CH2, C-6), 66.7 (CH2, CH2Ph), 128.1 (3 x CH, Ph), 128.5 (2 x CH, Ph), 136.6 (C, Ph), 156.5 (C, Cbz), 178.8 (C, C-i); vmax (cm1) 3331, 2944, 1687, 1527, 1252, 1140, 945.A solution of 6-aminocaproic acid (32.8 g, 0.25M) in 75 mL of HUnder ice-cooling, respectively, to the 6-aminocaproic acid (3.28g, 25mmol) in NaOH solution (3N, 10ml) Was added dropwise NaOH (4N, 10ml), CbzCl, basically the same rate, About 8min dropcomplete. 30min later, The reaction was stopped.The aqueous layer was extracted with ethyl acetate, Diversion layer pH = 3, Solid precipitated, filter, The filter cake was washed with ice water As a white solid, Vacuum dried overnight. 5.43g, yield 82percent[00271j Synthesis of 6-(((benzyloxy)carbonyl)amino)hexanoic acid. 6-Aminohexanoic acid (4.61 g, 35.17 mmol) was dissolved in a mixture of 15percent aqueous NaOH (100 mL) and dioxane (100 mL). After the mixture was cooled to 0°C, benzyl chloroformate (10 mL, 70.34 mmol) was added with vigorous stirring. The mixture was then stirred at room temperature for 2 days. The solvent was removed, the product mixture dissolved in water and acidified with acetic acid, and the product extracted into methylene chloride. The organic layer was dried with Na2SO4, filtered, and the solvent was removed. The product was purified by flash column chromatography using a gradient of heptane/ethyl acetate to give 81 percent (7.62 g).General procedure: To a cooled (0°C) solution of the appropriate amino acid (1 eq) in NaOH 2N, a solution of benzyl chloroformate (1.1 eq) was added dropwise. The mixture was kept under vigorous stirring for 30 min. The solution was then washed with Et

Molecular Weight:265.30
XLogP3:2
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:9
Exact Mass:265.13140809
Monoisotopic Mass:265.13140809
Topological Polar Surface Area:75.6
Heavy Atom Count:19
Complexity:275
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes