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

HRID 2351

반응식

HRID 2351 반응식
[C:1]1(=[O:28])[N:5]([CH:6]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH3:19])=[C:13]([O:20][CH2:21][CH3:22])[CH:12]=2)[CH2:7][C:8]([NH2:10])=O)[C:4](=[O:23])[C:3]2=[CH:24][CH:25]=[CH:26][CH:27]=[C:2]12.CN1CCOCC1.S(Cl)(Cl)=O.CC#N.OP(O)(O)=O.C([O-])(O)=O.[Na+]>CN(C=O)C>[C:4]1(=[O:23])[N:5]([CH:6]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH3:19])=[C:13]([O:20][CH2:21][CH3:22])[CH:12]=2)[CH2:7][C:8]#[N:10])[C:1](=[O:28])[C:2]2=[CH:27][CH:26]=[CH:25][CH:24]=[C:3]12

참가 물질

7

반응물 5

HCID 79724-MethylmorpholineHCID 24386Thionyl ChlorideHCID 516892Sodium BicarbonateHCID 100912883-Phthalimido-3-(3,4-diethoxyphenyl)propionamideHCID 22619319Acetonitrile phosphate

생성물 1

HCID 98419883-Phthalimido-3-(3,4-diethoxyphenyl)propionitrile수율 55%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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.

후처리

  1. temperatureTo an ice bath cooled
  2. stirringwas stirred at 0°-5° C. for 30 minutes and at room temperature for 2 hours
  3. filtrationThe mixture was filtered
  4. washthe solid was washed with copious amounts of H2O
  5. dissolutionThe wet solid was dissolved in CH2Cl2 (25 mL)
  6. customthe organic layer was separated
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo to a sticky semi-solid
  9. customThe solid was purified twice by flash column chromatography (silica gel, 3 % ethyl acetate/methylene chloride)
  10. customto afford a solid which
  11. customwas dried in vacuo (50° C., <1 mm)

출처 및 근거

ORD 기록
ord-e365fd6c4897470482774680a6343b87
출처 데이터셋
uspto-grants-1998_03
특허 번호
US05728845

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