HCID 66935459, compound → HCID 66935781, compound

HRID 1908794Notes

Reaction equation

HRID 1908794 reaction equation
[CH2:1]([O:3][C:4](=[O:17])[C:5]1[CH:10]=[C:9](Cl)[C:8]([N:12]([CH2:15][CH3:16])[CH2:13][CH3:14])=[N:7][CH:6]=1)[CH3:2].[CH2:18]([Zn]CC)[CH3:19]>O1CCOCC1.C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4](=[O:17])[C:5]1[CH:10]=[C:9]([CH2:18][CH3:19])[C:8]([N:12]([CH2:15][CH3:16])[CH2:13][CH3:14])=[N:7][CH:6]=1)[CH3:2]

Participants

5

Reactant 2

HCID 66935459HCID 66935459, compoundHCID 178418750HCID 178418750, compound2×

Product 1

HCID 66935781HCID 66935781, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 5-chloro-6-diethylamino-nicotinic acid ethyl ester (2.96 g, 11.5 mmol) in dioxane (50 mL), Pd(dppf) (470 mg, 0.576 mmol) is added under argon. To this mixture, diethyl zinc (8.53 g, 69.1 mmol, as a 1.1 M solution in toluene) is added dropwise. The mixture is stirred at 75° C. for 16 h before another portion of Pd(dppf) 94 mg, 0.115 mmol) and diethyl zinc (1.42 g, 11.5 mmol, as a 1.1 M solution in toluene) is added. Stirring is continued at 75° C. for 24 h. The reaction mixture is cooled to rt and carefully quenched with water. The mixture is filtered over celite and the filtrate is extracted twice with EA. The combined org. extracts are dried over MgSO4, filtered and concentrated. The crude product is purified by CC (heptane:EA 9:1) to give 6-diethylamino-5-ethyl-nicotinic acid ethyl ester (2.40 g) as a colourless oil; LC-MS: tR=0.78 min, [M+1]+=251.19; 1H NMR (CDCl3): δ 1.15 (t, J=7.0 Hz, 6H), 1.27 (t, J=7.3 Hz, 3H), 1.40 (t, J=7.3 Hz, 3H), 2.65 (q, J=7.5 Hz, 2H), 3.36 (q, J=7.0 Hz, 4H), 4.37 (q, J=7.0 Hz, 2H), 7.99 (d, J=2.3 Hz, 1H), 8.76 (d, J=2.3 Hz, 1H).

Workup

  1. customcarefully quenched with water
  2. filtrationThe mixture is filtered over celite
  3. extractionthe filtrate is extracted twice with EA
  4. dry with materialextracts are dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product is purified by CC (heptane:EA 9:1)

Sources & evidence

ORD record
ord-c681151879a74196ac490b0ef22697b0
Source dataset
uspto-grants-2013_12
Patent number
US08598208B2

Reaction notes

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