Pyridine → Methyl 3-(4-butoxyphenyl)-3-(2-cyanoacetamido)butanoate

HRID 1629800Notes

Reaction equation

HRID 1629800 reaction equation
[C:1]([CH2:3][C:4](O)=[O:5])#[N:2].C(Cl)(=O)C(Cl)=O.[NH2:13][C:14]([C:21]1[CH:26]=[CH:25][C:24]([O:27][CH2:28][CH2:29][CH2:30][CH3:31])=[CH:23][CH:22]=1)([CH3:20])[CH2:15][C:16]([O:18][CH3:19])=[O:17].N1C=CC=CC=1>C(Cl)Cl.CN(C=O)C>[CH2:28]([O:27][C:24]1[CH:23]=[CH:22][C:21]([C:14]([NH:13][C:4](=[O:5])[CH2:3][C:1]#[N:2])([CH3:20])[CH2:15][C:16]([O:18][CH3:19])=[O:17])=[CH:26][CH:25]=1)[CH2:29][CH2:30][CH3:31]

Participants

7

Reactant 4

HCID 1049PyridineHCID 9740Cyanoacetic acidHCID 65578Oxalyl chlorideHCID 86685893Methyl 3-amino-3-(4-butoxyphenyl)butanoate

Product 1

HCID 86685894Methyl 3-(4-butoxyphenyl)-3-(2-cyanoacetamido)butanoateYield 87%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 2-cyanoacetic acid (128 mg, 1.507 mmol) in CH2Cl2 (5 mL) was added oxalyl chloride (0.754 mL, 1.507 mmol) and 1 drop of DMF. The reaction was stirred at rt for 1 h and then concentrated. The resulting acid chloride was dissolved in CH2Cl2 (1 mL) and was then added to Intermediate 107C (200 mg, 0.754 mmol) and pyridine (0.183 mL, 2.261 mmol) in CH2Cl2 (5 mL). The reaction was stirred at rt for 5 h. The reaction mixture was concentrated and the residue was diluted with EtOAc. The organic layer was washed with saturated NH4Cl, dried over MgSO4, filtered and concentrated. The crude product was purified by silica gel chromatography (24 g silica gel, eluted with EtOAc in hexanes) to yield the desired product (218 mg, 87%) as a clear oil. 1H NMR (500 MHz, CDCl3) δ 7.22 (d, J=8.80 Hz, 2H), 6.85 (d, J=8.80 Hz, 2H), 3.94 (t, J=6.46 Hz, 2H), 3.65 (s, 3H), 3.30 (s, 2H), 3.03 (d, J=15.13 Hz, 1H), 2.85 (d, J=15.13 Hz, 1H), 1.80 (s, 3H), 1.71-1.78 (m, 2H), 1.44-1.53 (m, 2H), 0.97 (t, J=7.29 Hz, 3H).

Workup

  1. concentrationconcentrated
  2. dissolutionThe resulting acid chloride was dissolved in CH2Cl2 (1 mL)
  3. stirringThe reaction was stirred at rt for 5 h
  4. concentrationThe reaction mixture was concentrated
  5. additionthe residue was diluted with EtOAc
  6. washThe organic layer was washed with saturated NH4Cl
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by silica gel chromatography (24 g silica gel, eluted with EtOAc in hexanes)

Sources & evidence

ORD record
ord-ff9fd28f5077429a98e3275f96db56a2
Source dataset
uspto-grants-2014_07
Patent number
US08791091B2

Reaction notes

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