N,N'-BIS-TERT-BUTOXYCARBONYLTHIOUREA

White to off-white solid

General procedure: To a solution of thiourea(500 mg, 6.58 mmol) in dry tetrahydrofuran (120 mL) under argon at 0 °C wasadded a 60percent suspension of sodium hydride in mineral oil (1184 mg, 29.61 mmol).The reaction was stirred for 30 min at room temperature to complete formationof the anion and then cooled to 0 °C prior to addition of di-tert-butyl dicarbonate (3155 mg, 14.47 mmol). The reaction was stirred at RT overnight and then cooled to 0 °C. Dropwise water(20 mL) was added to quench the reaction. The aqueous phase was then extracted with EtOAc (3 x 50 mL). The combined organic phases were washed with brine (30 mL) and water (30 mL) and dried using anhydrous MgSOFirst, Compound 2 was obtained by reacting thioj0202]urea (Compound 1) with di-tert-butyl dicarbonate in thepresence of sodium hydride. Subsequently, after convertingCompound 2 into Compound 3 (see Yin B, et al., Tetrahedron Left., 49, 3687, 2008), Compound 4a (see Poss MA, etal., Tetrahedron Lett., 33, 5933, 1992) was obtained in ayield of 93percent by condensation of Compound 3 with hexTHF, ylamine in the presence of a water-soluble carbodiimide, andCompound 4b was obtained in a yield of 94percent by condensation of Compound 3 with dodecylamine. By reactingCompound 4a with a solution of hydrogen chloride ether, thecompound of (Compound No. 2) was obtained ina yield of 67percent. (Compound No. 2) 1H NMR (500 MHz, DMSO-d5)δ 8.10 (1H, bs), 7.79 (1H, bs), 7.56 (2H, bs), 7.41-7.27 (5H, m), 4.43 (2H, d, J=6.2 Hz), 3.15 (2H, q, J=6.8 Hz), 1.51-1.41 (2H, m), 1.32-1.21 (6H, m), 0.87 (3H, t, J=6.7 Hz).N, N'-t-Boc-protected thiourea: To a stirred solution of thiourea (0.57g, 7.5 mmol) in 150mL of THF under N2 at 0°C was added 60percent NaH (1.35g, 33.8 mmol) in mineral oil. After 5 minutes, the ice bath was removed and the reaction mixture was allowed to stir at room temperature for 10 minutes. The reaction mixture was cooled to 0°C and 3.6g (16.5mmol) of di-tert-butyl dicarbonate was added. After 30 minutes, the ice bath was removed and the reaction was stirred for 2h. The reaction was then quenched with saturated NaHCO3 solution, poured into water and extracted with 3x EtOAc. The organics were washed with H2O, brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue was triturated with hexane to provide 1.72g (83percent) of the desired product as a white solid.To a 250-mL neck round bottom flask was added thiourea(2 g, 26.27 mmol, 1, 100 equiv.) In tetrahydrofuran (50 mL)NaH 1 (60percent) (2.3 g) was then added in portions at -10 to 0 ° C with stirring.The resulting solution was stirred at -10 to 0 ° C for 1 hourTo this was added di-tert-butyl dicarbonate dropwise at 0 ° C and under stirring(12.6 g, 57.73 mmol, 2.20 equiv.) In tetrahydrofuran (50 mL)The resulting solution was stirred overnight at room temperature, The reaction was quenched by the addition of 100 mL of water, And then extracted with 2 x 100 mL of ethyl acetateThe combined organic layers were dried over anhydrous sodium sulfate and then concentrated in vacuoThe residue was purified on a silica gel column eluting with ethyl acetate: petroleum ether (1: 5-1: 2) to give 1.58 (21percent)Tert-butyl ^ ([[(tert-butoxy) carbonyl] amino] thiomethylene) carbamate tert-butyl N-({[(tert-butoxy)carbonyl]amino}methanethioyl)carbamate as a white solid.To a stirred solution of NaH (1.35 g, 33.8 mmol) (60percent suspension in mineral oil) in dry THF (150 mL), under inert conditions at 0 °C, was added thiourea (0.570 g, 7.5 mmol) portionwise over 5 min, and left to stir at room temperature for 15 min. Following cooling to 0 °C, di-tert-butyl carbonate (3.60 g, 16.5 mmol) was added, and stirring was continued for 40 min, prior to warming to room temperature over 3 h. The reaction was subsequently quenched via the addition of saturated aqueous NaHCO1.3-Di-(tert-butoxycarbonyl)thiourea (1)

Molecular Weight:276.35
XLogP3:3.4
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:4
Exact Mass:276.11437830
Monoisotopic Mass:276.11437830
Topological Polar Surface Area:109
Heavy Atom Count:18
Complexity:310
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes