تفاعل #52027

معادلة التفاعل

chlorosulfonyl isocyanate

3,5-Dimethylbenzoic acid

intermediate ( 2 )

N-benzyl-N-{[4-({[tert -butyl(dimethyl)silyl]oxy}methyl)cyclohexyl]methyl}sulfamide

triethylamine

→

title compound

المردود 86.0%

N-benzyl-N-{[4-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclohexyl]methyl}-N′-(3,5-dimethylbenzoyl)sulfamide

المردود 86.0%

المذيبات

dichloromethane

dichloromethane

—

hexanes

dichloromethane

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةheated
2. 2
   درجة الحرارةto reflux
3. 3
   أخرىReaction mixture
4. 4
   درجة الحرارةof reflux
5. 5
   أخرىto evaporate when solid
6. 6
   أخرىprecipitated out
7. 7
   أخرىRecovered
8. 8
   ترشيحfiltered solid
9. 9
   أخرىReaction
10. 10
    workup.WAITwas complete at 2 hours, at which point it
11. 11
    أخرىwas purified directly by silica gel chromatography

الإجراء التجريبي

3,5-Dimethylbenzoic acid (1.50 g, 10.0 mmole, 1.0 eq) was suspended in 5 mL dichloromethane and heated to reflux, after which a solution of chlorosulfonyl isocyanate (0.87 mL, 10.0 mmole, 1.0 eq) in 2 mL dichloromethane was added. Reaction mixture became clear, and remained so after 40 minutes of reflux. Cooled to room temperature, added hexanes and began to evaporate when solid precipitated out. Recovered filtered solid. 23 mg, 92 μmole, 1.0 eq of this material was added to a mixture of intermediate (2) (34 mg, 92 μmole, 1.0 eq) and triethylamine (39 μL, 277 μmole, 3.0 eq) in dichloromethane (0.5 mL). Reaction was complete at 2 hours, at which point it was purified directly by silica gel chromatography to give the title compound in 86% yield. 1H NMR (500 MHz, DMSO-d6): δ 11.84 (s, 1H), 7.49 (s, 2H), 7.31 (m, 6H), 4.52 (s, 2H), 3.28 (d, 2H), 3.09 (d, 2H), 2.30 (s, 6H), 1.58 (m, 4H), 1.31 (m, 1H), 1.22 (m, 1H), 0.82 (s, 9H), 0.66 (m, 4H), 0.04 (s, 6H). N-benzyl-N′-(3,5-dimethylbenzoyl)-N-{[4-(hydroxymethyl)cyclohexyl]methyl}sulfamide (38): Intermediate (37) was treated as (3) was treated in the synthesis of (4) to give the title alcohol in quantitative yield. 1H NMR (500 MHz, DMSO-d6): δ 11.85 (s, 1H), 7.50 (s, 2H), 7.31 (m, 6H), 4.52 (s, 2H), 4.27 (t, 1H), 3.10 (m, 4H), 2.32 (s, 6H), 1.59 (m, 4H), 1.31 (m, 1H), 1.22 (m, 1H), 0.66 (m, 4H). {4-[(benzyl{[(3,5-dimethylbenzoyl)amino]sulfonyl}amino)methyl]cyclohexyl}methyl phenylcarbamate (39): Alcohol (38) (34.6 mg, 78 mmole, 1.0 eq) in 0.5 mL dichloromethane was treated with triethylamine (38 mL, 272 mmole, 3.5 eq) and phenyl isocyanate (17 mL, 156 mmole, 2.0 eq) to give the title compound after preparative TLC. 1H NMR (500 MHz, DMSO-d6): δ 11.85 (s, 1H), 9.52 (s, 1H), 7.50 (s, 2H), 7.41 (d, 2H), 7.36 (d, 2H), 7.30 (t, 2H), 7.24 (t, 3H), 7.19 (s, 1H), 6.95 (t, 1H), 4.48 (s, 2H), 3.800 (d, 2H), 3.07 (d, 2H), 2.32 (s, 6H), 1.64 (m, 4H), 1.47 (m, 1H), 1.34 (m, 1H), 0.73 (m, 4H).

المصدر