反応 #1896242

反応方程式

4-(4-Carboxy-thiophen-2-yl)-piperidine-1-carboxylic acid t-butyl ester

Triethylamine

HATU

2-phenylpiperidine

→

title compound

収率 51.1%

(2-Phenyl-piperidin-1-yl)-(5-piperidin-4-yl-thiophen-3-yl)methanone

収率 51.1%

溶媒

trifluoroacetic acid

DCM

acetonitrile

反応条件

後処理

1. 1
   その他The mixture was purified by HPLC
2. 2
   洗浄eluting with 10%-98% acetonitrile in water (0.1% formic acid) over 30 minutes
3. 3
   workup.ADDITIONThe fractions containing the desired product
4. 4
   濃縮were concentrated under vacuum
5. 5
   その他to give an oil which
6. 6
   その他The solvent was evaporated
7. 7
   その他the residue was purified by flash chromatography on an SCX-2 cartridge
8. 8
   洗浄washing with acetonitrile
9. 9
   洗浄methanol and then eluting with 2 M ammonia in methanol
10. 10
    workup.ADDITIONThe fractions containing the desired product
11. 11
    濃縮were concentrated under vacuum

実験手順

4-(4-Carboxy-thiophen-2-yl)-piperidine-1-carboxylic acid t-butyl ester (0.1 g, 0.32 mmol) was dissolved in acetonitrile (2 mL). Triethylamine (0.96 mmol), HATU (0.35 mmol) and 2-phenylpiperidine (0.35 mmol) were added and the reaction stirred at room temperature for 5 hours. The mixture was purified by HPLC, eluting with 10%-98% acetonitrile in water (0.1% formic acid) over 30 minutes. The fractions containing the desired product were concentrated under vacuum to give an oil which was dissolved in trifluoroacetic acid (3 mL) and DCM (5 mL) and stirred for 3 hours. The solvent was evaporated and the residue was purified by flash chromatography on an SCX-2 cartridge, washing with acetonitrile, then methanol and then eluting with 2 M ammonia in methanol. The fractions containing the desired product were concentrated under vacuum to give the title compound (0.058 g). LCMS m/z 355.18 [M+H]+ RT=6.59 min (Analytical Method 2). 1H NMR (400 MHz, CHCl3-d): δ 7.4 (m, 2H), 7.25 (m, 4H), 6.9 (s, 1H), 3.2 (d, 2H), 2.9 (m, 2H), 2.7 (m, 2H), 2.6 (m, 3H), 2.4 (d, 1H), 2.1-1.8 (m, 3H), 1.8-1.4 (m, 6H).

出典