N-tert-Butoxycarbonyl-L-tert-leucine

White crystalline powder

2(S)-tert-Butoxycarbonylamino-3, 3-dimethyl-butyric Acid To a suspension of L-tert-leucine (26.1 g, 0.2 mol) in methanol (150 mL) was added triethylamine (56 mL, 0.4 mol) and the mixture cooled to 0 C. To the mixture was added slowly a solution: of di-tert-butyldicarbamate (48 g, 0.22 mol) in methanol (40 mL) such that an internal temperature of between 0 and 5 C. was maintained. The reaction was allowed to stir overnight and the solvents were removed in vacuo. The residue was dissolved in ethyl acetate (200 mL) and washed with 10percent w/v aqueous citric acid solution (3100 mL). The organic layer was dried over MgSO4, filtered and the solvents removed in vacuo to give the title product as a pale yellow oil (48.9 g, >100percent, residual solvent). 1H NMR (CDCl3): ?/ppm 9.20 (1H, bs), 5.10 (1H, m), 4.15 (1H, m), 1.45 (9H, s), 1.00 (9H, s).(1) adding sodium hydroxide, L-tert-leucine and water according to a molar ratio of 1: 1: 10 into a reactor, Then, an equimolar amount of (Boc) 2O and L-tert-leucine were dissolved in 10 times of 1, 4-dioxane, Slowly dripped into the reactor, stirred at room temperature for 12 hours after dripping finished, after the solvent was concentrated to half and the same volume of ethyl acetate was added and the reaction solution was concentrated, then added 4mol / L hydrochloric acid half of the volume of ethyl acetate, liquid separation , The organic phase was washed once with an equal volume of water, dried over anhydrous sodium sulfate and evaporated to give the compound 5, the structure is shown in Formula 8;Triethylamine (890 uL, 6.40 mmol) was added dropwise to a stirred solution of L-tert- leucine (300 mg, 2.29 mmol) and di-tert-butyl dicarbonate (599 mg, 2.74 mmol) in dioxane/water 1: 1 (8 mL) and the solution was stirred overnight. The mixture was extracted with petroleum ether (2x) and the aqueous phase was cooled to 0 °C and carefully acidified to pH 3 by slow addition of 4M NaHS04 H20. The acidified water phase was extracted with EtOAc (3x) and the combined organic phases were washed with brine (2x) and was then dried, filtered and concentrated to give compound 36 (522 mg, 99 percent) as a colorless powder. No further purification was needed. 1H-NMR (300 MHz, CD30D) 8 0.99 (s, 9H), 1.44 (s, 9H), 3.96 (s, 1H); 13C-NMR (75.5 MHz, CD30D) 5 27.1, 28.7, 34.9, 68.0, 80.5, 157.8, 174.7.Example 20 An aqueous solution (1150 g) containing L-tert-leucine (100 g, 762 mmol) was stirred, and the pH of the solution was adjusted to 9 using a 30percent by weight of sodium hydroxide aqueous solution. Then, isopropanol (160 g) was added thereto. Further, di-tert-butyl dicarbonate (174.7 g, 800 mmol) was added thereto at 25°C with maintaining the pH between 8.5 and 9.5 using a 30percent by weight of sodium hydroxide aqueous solution. The mixture was stirred for about 3 hours, and the resultant was analyzed; as a result, 175 g of N-tert-butoxycarbonyl-L-tert-leucine was produced (yield: 99percent).Example 17 An aqueous solution (250.5 g) containing L-tert-leucine (20.5 g, 0.16 mol) was cooled to 7°C, and a 48percent by weight of sodium hydroxide aqueous solution (16.5 g) was added thereto. Then, di-tert-butyl dicarbonate (34.92 g, 0.16 mol, 1.00 equivalent) was slowly added with maintaining the pH in 9.4-10.8. After the addition, the mixture was stirred at not more than 20°C for 14 hours. Then, the yield and the amount of the generated impurity were analyzed by HPLC. Yield: 96percent, Reaction selectivity: 98percent The reaction was carried out in the same conditionStep 6: Preparation of N-(tert-Butoxycarbonyl)-L-tert-leucine; To a suspension of L-tert-leucine (5.0 g, 38 mmol) in dioxane (50 mL) and HPreparation of N-(tert-Butoxycarbonyl)-L-tert-leucine (MD009) Example 8 In a four-neck flask, 10.0 g (1.0 eq) of N-Boc-t-butyl ethylamine alcohol compound was added. Isopropyl acetate 100ml, sodium bromide 2.0eq, sodium bicarbonate 2.0eq, TMEPO 0.05eq, Cool to 0-5 °C. Temperature control 0 ~ 5 °C, sodium hypochlorite drops 1.2eq, about 1.0 ~ 1.5h drops, heat 2h, Warm up to 20 ~ 25 °C, heat 1.0 ~ 2.0h. Sodium thiosulfate solid 0.6 eq was added and incubated for 0.5 h. The aqueous layer was further extracted with 20 ml isopropyl acetate and the phases separated. Add 20 ml of isopropyl acetate to the aqueous layer, add citric acid, adjust the pH to 2 to 3, separate the phases, extract the aqueous layer with 20 ml of x 2 isopropyl acetate, combine the organic layers, add 50 ml of water to wash, separate the phases, and then apply the organic layer. Dry with 0.5g anhydrous magnesium sulfate 0.5h, suction filtration, the filtrate was evaporated to dryness at 40 ~ 50 °C, 40 ~ 50 °C insulation, 5ml of isopropyl acetate was added, 25ml of heptane was added dropwise, slowly cooling and crystallization, 20 ~ 30 °C heat 0.5h, suction filtration, washing, 7.8g boutique, yield 73percent. Optical purity 100percent.

Protected amino acid.

Molecular Weight:231.29
XLogP3:2.3
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:5
Exact Mass:231.14705815
Monoisotopic Mass:231.14705815
Topological Polar Surface Area:75.6
Heavy Atom Count:16
Complexity:273
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes