反応 #57449

反応方程式

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

収率 89.0%

溶媒

dichloromethane

反応条件

後処理

1. 1
   その他the reaction solvent was removed in vacuo
2. 2
   その他the residue was purified on a preparative TLC plate (20×20 cm, 500 μM)
3. 3
   洗浄eluting with 96:4 methylene chloride
4. 4
   その他The product band was removed
5. 5
   洗浄eluted with 4:1 methylene chloride
6. 6
   ろ過methanol, filtered
7. 7
   その他evaporated in vacuo
8. 8
   その他The residue was triturated from diethylether and hexane
9. 9
   その他the solvents were evaporated in vacuo

実験手順

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).

出典