반응 #2447

반응 방정식

CH3CN H3PO4

NaHCO3

3-phthalimido-3-(3,4-diethoxyphenyl)propionamide

4-methylmorpholine

thionyl chloride

→

product

수율 55.0%

3-Phthalimido-3-(3,4-diethoxyphenyl)propionitrile

수율 55.0%

용매

DMF

반응 조건

후처리

1. 1
   온도To an ice bath cooled
2. 2
   workup.STIRRINGwas stirred at 0°-5° C. for 30 minutes and at room temperature for 2 hours
3. 3
   여과The mixture was filtered
4. 4
   세척the solid was washed with copious amounts of H2O
5. 5
   workup.DISSOLUTIONThe wet solid was dissolved in CH2Cl2 (25 mL)
6. 6
   기타the organic layer was separated
7. 7
   건조dried over MgSO4
8. 8
   농축concentrated in vacuo to a sticky semi-solid
9. 9
   기타The solid was purified twice by flash column chromatography (silica gel, 3 % ethyl acetate/methylene chloride)
10. 10
    기타to afford a solid which
11. 11
    기타was dried in vacuo (50° C., <1 mm)

실험 절차

To an ice bath cooled stirred suspension of 3-phthalimido-3-(3,4-diethoxyphenyl)propionamide (0.96 g, 2.5 mmol) and 4-methylmorpholine (0.66 mL, 6 mmol) in DMF (9 mL) under nitrogen, was added thionyl chloride (0.35 mL, 4.8 mmol) dropwise. There was a slight exotherm after which the mixture was stirred at 0°-5° C. for 30 minutes and at room temperature for 2 hours. The reaction was monitored by HPLC (Waters Nova-Pak/C-18 column, 3.9×150 mm, 4 micron, 1 mL/min, 240 nm, 50/50 CH3CN/H3PO4 0.1% (aq)). The reaction mixture was poured into a mixture of NaHCO3 (8.5 mL) and ice (40 g) and stirred until the ice had melted. The mixture was filtered and the solid was washed with copious amounts of H2O. The wet solid was dissolved in CH2Cl2 (25 mL) and the organic layer was separated and dried over MgSO4 and concentrated in vacuo to a sticky semi-solid. The solid was purified twice by flash column chromatography (silica gel, 3 % ethyl acetate/methylene chloride) to afford a solid which was dried in vacuo (50° C., <1 mm) to afford 0.5 g (55%) of product as a pale yellow solid; 1H NMR (CDCl3) δ7.91-7.65(m, 4H), 7.12-6.98(m, 2H), 6.90-6.78(m, 1H), 5.61(dd, J=6.4, 10.3 Hz, 1H), 4.19-3.96(m, 4H), 3.83(dd, J=10.3, 16.8 Hz, 1H), 3.26(dd, J=6.4, 16.8 Hz, 1H), 1.55-1.30(m, 6H); 13C NMR (CDCl3)δ167.7, 149.2, 148.9, 134.3, 131.5, 129.1, 123.6, 120.2, 116.9, 113.2, 112.9, 64.7, 64.5, 51.1, 21.1, 14.7; HPLC 98.4%. Anal. Calcd for C21H20N2 O4. Theoretical: C, 69.22; H,5.53; N,7.69. Found: C, 69.06; H, 5.48; N, 7.58.

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