N,N'-Dimethyl-1,2-cyclohexanediamine

Clear colorless to slightly yellow liquid

Epoxycyclohexane (98.2 g, 1.0 mol) was placed in a reaction flask with a balloon buffer seal.Mix with 35percent aqueous methylamine (1.0 mole) followed by the addition of 2.5 grams of inorganic boric acid catalyst, The reaction was heated to 50°C for 2 hours and the reaction was completed. Cool to 0°CAdd 0percent sulfuric acid solution (1.0 mol) dropwise to the above reaction solution.The temperature control does not exceed 40°C during the entire dropwise addition.The temperature is raised to 110°C under atmospheric pressure to remove water under stirring.When the water no longer flows out, the reaction system gradually becomes sticky.After adding 85 ml of sulfolane, it was changed to vacuum distillation.At this point, the reaction temperature is gradually increased to a final temperature of 140° C., and the vacuum is drawn for 7-8 hours.Detection of water 0.38percent. The reaction solution was cooled to 0°C.Aqueous sodium hydroxide solution was added dropwise to adjust pH=12-13.Start warming slowly with gradual stirring, when heated to 75°C, The reaction solution gradually clarified. At this time, the detection ring was completely cooled to room temperature.81.9 grams of the upper layer liquid was separated, and the GC content was 95.2percent. The yield of the first two steps was 70percent.In the autoclave, the above liquid, 35percent methylamine aqueous solution (1.12 mol) was addedAnd 1.4 g inorganic boric acid, heated to 90 ° C, sealed overnight, the reaction was completed (recovery of external standard yield 96percent), after cooling, vacuum distillation to remove water and part of the front distillate, to receive cyclohexane dimethylamine pure product After distilling, the front distillate was combined to give a total of 88.6 g of a colorless liquid.The yield is 89percent. After cooling, it turns into an almost white solid GC: 99.2percent.Step 2. tert-Butyl methyl((1S, 2S)-2-(methylamino)cyclohexyl)carbamate (23-3) (1S, 2S)-N1, N2-dimethylcyclohexane-1, 2-diamine ((S, S)-1-5a, 1 g, 7.03 mmol) was added to a solution of conc. HCl (0.58 mL, 7.03 mmol) and MeOH (15 mL) at 0 C. The resulting solution was then warmed to room temperature and Boc anhydride (1.63 mL, 7.03 mmol) in MeOH (15 mL) was added dropwise over 20 min. The reaction mixture was stirred overnight, concentrated, and then treated with 1 M aq. NaOH to bring the pH to 8-9. The resulting mixture was then extracted with DCM (3*30 mL) and the combined organic phases were washed with brine, dried over sodium sulfate, filtered, and concentrated. The crude product was purified by reverse phase RP-C18 column chromatography eluting with 10 to 80% MeCN in water with 0.1% NH4OH as a modifier to provide the desired product 23-3 (665 mg, 2.74 mmol, 39% yield) as a white solid. MS [M+H]+=243.2.Step 2. tert-Butyl methyl((1S, 2S)-2-(methylamino)cyclohexyl)carbamate (23-3) (1S, 2S)-N1, N2-dimethylcyclohexane-1, 2-diamine ((S, S)-1-5a, 1 g, 7.03 mmol) was added to a solution of conc. HCl (0.58 mL, 7.03 mmol) and MeOH (15 mL) at 0 C. The resulting solution was then warmed to room temperature and Boc anhydride (1.63 mL, 7.03 mmol) in MeOH (15 mL) was added dropwise over 20 min. The reaction mixture was stirred overnight, concentrated, and then treated with 1 M aq. NaOH to bring the pH to 8-9. The resulting mixture was then extracted with DCM (3*30 mL) and the combined organic phases were washed with brine, dried over sodium sulfate, filtered, and concentrated. The crude product was purified by reverse phase RP-C18 column chromatography eluting with 10 to 80% MeCN in water with 0.1% NH4OH as a modifier to provide the desired product 23-3 (665 mg, 2.74 mmol, 39% yield) as a white solid. MS [M+H]+=243.2.

N,N''-Dimethyl-1,2-cyclohexanediamine is used as a catalyst in the synthesis of substituted pyrazoles with anti-inflammatory activity. As well as highly functional pyridines and bipyridines.

Molecular Weight:142.24
XLogP3:0.7
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:142.146998583
Monoisotopic Mass:142.146998583
Topological Polar Surface Area:24.1
Heavy Atom Count:10
Complexity:81.3
Undefined Atom Stereocenter Count:2
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes