تفاعل #57449

معادلة التفاعل

o-Toluoyl chloride

N1-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N1-(cyclopentyloxy)-4-methoxy-1-benzenesulfonamide

trifluoracetic acid

N,N-diisopropylethylamine

→

N1-((1S,2R)-1-benzyl-3-(cyclopentyloxy)[(4-methoxyphenyl)sulfonyl]amino-2-hydroxypropyl)-2-methylbenzamide

المردود 89.0%

المذيبات

dichloromethane

ظروف التفاعل

المعالجة

1. 1
   أخرىthe reaction solvent was removed in vacuo
2. 2
   أخرىthe residue was purified on a preparative TLC plate (20×20 cm, 500 μM)
3. 3
   غسيلeluting with 96:4 methylene chloride
4. 4
   أخرىThe product band was removed
5. 5
   غسيلeluted with 4:1 methylene chloride
6. 6
   ترشيحmethanol, filtered
7. 7
   أخرىevaporated in vacuo
8. 8
   أخرىThe residue was triturated from diethylether and hexane
9. 9
   أخرىthe solvents were evaporated in vacuo

الإجراء التجريبي

o-Toluoyl chloride (7.8 μL, 0.0602 mmol) was added to a solution of N1-[(2R,3S)-3-amino-2-hydroxy-4-phenylbutyl]-N1-(cyclopentyloxy)-4-methoxy-1-benzenesulfonamide×trifluoracetic acid (Step 1, Example 48), (30 mg, 0.055 mmol) and N,N-diisopropylethylamine (23.8 μL, 0.137 mmol) in approximately 1.5 mL of dichloromethane under Argon. After stirring for 18 hours at ambient temperature, the reaction solvent was removed in vacuo and the residue was purified on a preparative TLC plate (20×20 cm, 500 μM) eluting with 96:4 methylene chloride:methanol. The product band was removed, eluted with 4:1 methylene chloride:methanol, filtered, and evaporated in vacuo. The residue was triturated from diethylether and hexane and the solvents were evaporated in vacuo to provide N1-((1S,2R)-1-benzyl-3-(cyclopentyloxy)[(4-methoxyphenyl)sulfonyl]amino-2-hydroxypropyl)-2-methylbenzamide (27 mg, 89%) as a solid. H1-NMR (dimethylsulfoxide-D6): 1.75 (m, 8H), 1.87 (s, 3H), 2.63 (m, 1H), 2.79 (bm, 1H), 3.05 (bm, 1H), 3.21 (bm, 1H), 3.69 (bm, 1H), 3.86 (s, 3H), 4.13 (bm, 1H), 4.86 (bm, 1H), 5.28 (bs, 1H), 6.79 (m, 1H), 7.21 (m, 10H), 7.72 (d, 2H), 8.06 (d, 1H). MS(ESI): 575(M+Na).

المصدر