N-methyl-2-pyrrolidone → HCID 67026957, compound

HRID 1908722Notes

Reaction equation

HRID 1908722 reaction equation
[CH2:1]([O:3][C:4](=[O:12])[C:5]1[CH:10]=[CH:9][N:8]=[C:7](Cl)[CH:6]=1)[CH3:2].CN1C(=O)CCC1.[CH2:20]([Mg]Br)[CH:21]([CH3:23])[CH3:22]>C1COCC1>[CH2:1]([O:3][C:4](=[O:12])[C:5]1[CH:10]=[CH:9][N:8]=[C:7]([CH2:20][CH:21]([CH3:23])[CH3:22])[CH:6]=1)[CH3:2]

Participants

5

Reactant 3

HCID 13387N-methyl-2-pyrrolidoneHCID 2762942Ethyl 2-chloroisonicotinateHCID 178418816HCID 178418816, compound

Product 1

HCID 67026957HCID 67026957, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-75 °C

Procedure

To a solution of 2-chloro-isonicotinic acid ethyl ester (10.0 g, 63.3 mmol) in THF (150 mL), NMP (8.78 g, 88.6 mmol) and Fe(acac)3 (2.46 g, 6.96 mmol) is added under argon. The mixture is cooled to −74° C. before isobutylmagnesium bromide (47 mL of a 2 M solution in THF, 94.9 mmol) is added. The temperature rises to −65° C. The mixture is stirred at −75° C. for 1 h, then warmed to rt and carefully quenched with water. The mixture is extracted with EA, the org. extract is dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 9:1 to give 2-isobutyl-isonicotinic acid ethyl ester (3.00 g) as an oil, LC-MS: tR=0.74 min, [M+1]+=208.11.

Workup

  1. additionis added
  2. customrises to −65° C
  3. temperaturewarmed to rt
  4. customcarefully quenched with water
  5. extractionThe mixture is extracted with EA
  6. extractionextract
  7. dry with materialis dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product is purified by CC on silica gel eluting with heptane:EA 9:1

Sources & evidence

ORD record
ord-7169f9be2c244d3287e3933e195c45ca
Source dataset
uspto-grants-2013_12
Patent number
US08598208B2

Reaction notes

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