Electric Literature of 645-00-1, A common heterocyclic compound, 645-00-1, name is 1-Iodo-3-nitrobenzene, molecular formula is C6H4INO2, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
To a mixture of 3-iodonitrobenzene (7 g, 28.1 mmoles), K2CO3 (11.63 g, 84.3 mmoles) in 80 mL 1,2-DME/water (1: 1) were added successively CuI (229.50 mg, 1.21 mmoles), PPH3 (591.20 mg, 2.25 mmoles), Pd/C 10% (598. 0 mg, 0.562 mmoles). The mixture was stirred at room temperature for 1 hour. 4-BUTYN-1-OL (5.90 g, 84.30 mmoles) was added, then the mixture was heated to reflux overnight. After cooling, the mixture was filtered on Celite and the organic layer was evaporated under reduced pressure. Tha aqueous layer was acidified with concentrated Chlorhydric acid and extracted with AcOEt. The organic layer were washed with brine, dried, filtered and evaporated. Purified by flash CHNNATOGRAPHY on silica gel AcOEt/Hexanes (35: 65). Yield: 81% H NMR (CDC13,300 MHz) 8 : 8.29 (s, Ar, 1H), 8.17 (M, Ar, 1H), 7.74 (d, Ar, 1H, J = 8HZ), 7.51 (t, Ar, 1H, J = 8Hz), 4.53 (d, 2H, J = 6Hz). A mixture of 3-(3-nitrophenyl)-prop-2-yn-1-ol (100 mg, 0.564 mmoles), Pd/C 10% (10 mg, 0.094 mmoles) was hydrogenated under 38 psi overnight. The mixture was filtered on Celite and the filtrate was evaporated to dryness. Purified by flash chrmatography on silica gel AcOEt/Hexanes (25: 75). Yield: 99% H NMR (CDC13, 300 MHz) 8 : 7.08 (t, Ar, 1H, J = 8. 0Hz), 6.61 (d, Ar, 1H, J = 7. 5HZ), 6.53 (M, Ar, 2H), 3.67 (t, 2H, J = 6. 5HZ), 2.84 (s, 3H), 2.62 (t, 2H, J = 8. 0Hz), 1.87 (M, 2H). 3-(3-aminophenyl)propan-1-ol was then reacted with 2-chloroethylisocyanate as described in examples 1-12 to obtain desired product. Purified by flash chromatography on silica gel ETOH/CH2CL2 (2: 98).EXAMPLE 45: Preparation of Acetic acid 3- {3- [3- (2-CHLORO-ETHYL)-UREIDO]-PHENYL}-PROPYL ester (42) To a mixture OF 3-IODONITROBENZENE (1 g, 4.56 mmoles), K2CO3 (1.57 g, 11.4 mmoles) in 30 mL 1.2-DME/water (1: 1) were added successively CuI (34.78 mg, 0. 18 mmoles), PPH3 (95.80 mg, 0.36 mmoles), Pd/C 10% (97.05 mg, 0.09 mmoles). The mixture was stirred at room temperature for 1 hour. Propargyl alcohol (807 mg, 14.40 mmoles) was added, then the mixture was heated to reflux overnight. After cooling, the mixture was filtered on Celite and the organic layer was evaporated under reduced pressure. Tha aqueous layer was acidified with concentrated Chlorhydric acid and extracted with AcOEt. The combined organic layers were washed with brine, dried, filtered and evaporated. Purified by flash chromatography on silica gel CH2CL2/ETOH (95: 5). Yield: 81% IH NMR (CDC13, 300 MHz) 8 : 8.29 (s, Ar, 1H), 8.17 (M, Ar, 1H), 7.74 (d, Ar, 1H, J = 8HZ), 7.51 (t, Ar, 1H, J = 8Hz), 4.53 (d, 2H, J = 6Hz). To an ice-cold 3- (3-NITROPHENYL)-PROP-2-YN-L-OL (150 mg, 0.85 mmoles) in diethylether (10 mL) were added acetic anhydride (254.23 mg, 2.54 mmoles), triethylamine (256.54 mg, 2.54 mmoles), 4-pyrrolidinopyridine (2.52 mg, 0.017 mmoles) and the mixture was stirred at room temperature for 12 hours. The reaction was quenched by saturated solution OF NA2C03 and the mixture was extracted with AcOEt. The extracts were washed with brine, dried and evaporated. Purified by flash chromatography on silica gel AcOEt/Hexanes (8 : 2). Yield: 99% IH NMR (CDC13, 300 MHz) 8 : 8.24 (s, Ar, 1H), 8.14 (d, Ar, 1H, J = 8. 5HZ), 7.71 (d, Ar, 1H, J = 7. 5HZ), 7. 48 (t, Ar, 1H, J= 8HZ), 4. 88 (s, 2H), 2.12 (s, 3H). A mixture of acetic acid 3- (3-NITROPHENYL)-PROP-2-YNYL ester (100 mg, 0.48 mmoles), Pd/C 10% (10 mg, 0.094 mmoles) in 30 mL of dry ethanol was hydrogenated under 38 psi overnight. The mixture was filtered on Celite and the filtrate was evaporated to dryness. Purified by flash chromatography on silica gel AcOEt/Hexanes (25: 75). Yield: 81% IH NMR (CDC13,300 MHz) 8 : 7.08 (m, Ar, 1H), 6.59 (d, Ar, 1H, J = 7. 5HZ), 6.53 (m, Ar, 2H), 4.09 (t, 2H, J = 6. 5HZ), 3.66 (s, 2H), 2.60 (t, 2H, J = 8HZ), 2.06 (s, 3H), 1.93 (M, 2H). Acetic acid 3- (3-AMINOPHENYL)-PROP-2-YNYL ester was then reacted with 2-chloroethylisocyanate as described in examples 1-12 to obtain desired product. Purified by flash chromatography on silica gel ACOET/CH2CL2 (2: 8). Yield: 93%
The basis of chemical reaction formula synthesis, the synthesis route is composed of some specific reactions and combined according to certain logical thinking. We look forward to the emergence of more reaction modes in the future.
Reference:
Patent; IMOTEP INC.; WO2004/106291; (2004); A1;,
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com