Tetrahydrofuran → HCID 67027192, compound

HRID 2040781Notes

Reaction equation

HRID 2040781 reaction equation
[CH:1]([O:4][C:5](=[O:14])[C:6]1[CH:11]=[C:10]([CH3:12])[N:9]=[C:8](Cl)[CH:7]=1)([CH3:3])[CH3:2].[Br-].[CH2:16]([CH:18]([Zn+])[CH2:19][CH3:20])[CH3:17].C1COCC1>O1CCOCC1>[CH:1]([O:4][C:5](=[O:14])[C:6]1[CH:11]=[C:10]([CH3:12])[N:9]=[C:8]([CH:18]([CH2:19][CH3:20])[CH2:16][CH3:17])[CH:7]=1)([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 866398782-Chloro-6-methyl-isonicotinic acid isopropyl esterHCID 178456109HCID 178456109, compound

Product 1

HCID 67027192HCID 67027192, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 2-chloro-6-methyl-isonicotinic acid isopropyl ester (2.0 g, 9.36 mmol) in dioxane (75 mL) is degassed and put under argon before Pd(dppf) (229 mg, 0.281 mmol) is added. At rt, a 0.5 M solution of 1-ethyl-propylzinc bromide in THF (46.8 mL, 23.4 mmol) is added dropwise to the mixture. The mixture is stirred at 80° C. for 16 h before the reaction is quenched by adding ice-cold water (200 mL). A precipitate forms and the mixture is diluted with EA (200 mL) and filtered through celite. The filtrate is transferred into a separatory funnel. The org. phase is collected and the aq. phase is extracted with EA (120 mL). The combined org. extracts are dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 9:1 to 4:1 to give 2-(1-ethyl-propyl)-6-methyl-isonicotinic acid isopropyl ester (1.6 g) as a yellow oil; LC-MS: tR=0.79 min, [M+1]+=250.14; 1H NMR (D6-DMSO): δ 0.70 (t, J=7.3 Hz, 6 H), 1.33 (d, J=6.3 Hz, 6 H), 1.58-1.70 (m, 4 H), 2.51 (s, 3 H), 2.55-2.63 (m, 1 H), 5.15 (hept, J=5.8 Hz), 7.39 (s, 1 H), 7.49 (s, 1 H).

Workup

  1. additionis added
  2. customis quenched
  3. additionby adding ice-cold water (200 mL)
  4. additionA precipitate forms and the mixture is diluted with EA (200 mL)
  5. filtrationfiltered through celite
  6. customThe filtrate is transferred into a separatory funnel
  7. customphase is collected
  8. extractionthe aq. phase is extracted with EA (120 mL)
  9. dry with materialextracts are dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe crude product is purified by CC on silica gel eluting with heptane:EA 9:1 to 4:1

Sources & evidence

ORD record
ord-257ae880b40e4c0582a3700fe8335085
Source dataset
uspto-grants-2013_11
Patent number
US08580824B2

Reaction notes

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