Hydrochloric Acid → HCID 66933484, compound

HRID 1908841Notes

Reaction equation

HRID 1908841 reaction equation
[CH:1]([O:4][C:5]([C:7]1[CH:12]=[CH:11][C:10](Br)=[C:9]([CH3:14])[N:8]=1)=[O:6])([CH3:3])[CH3:2].Cl.O1CCO[CH2:18][CH2:17]1>CC(=O)OCC.C[CH2-].C[CH2-].[Zn+2]>[CH:1]([O:4][C:5]([C:7]1[CH:12]=[CH:11][C:10]([CH2:17][CH3:18])=[C:9]([CH3:14])[N:8]=1)=[O:6])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 66933380HCID 66933380, compound

Product 1

HCID 66933484HCID 66933484, compound

Reagents, catalysts & solvents 2

HCID 11185557-20-0CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Diethyl zink (9.78 g, 79.2 mmol) is added to a solution of 5-bromo-6-methyl-pyridine-2-carboxylic acid isopropyl ester (14.6 g, 56.5 mmol, prepared in analogy to 5-bromo-6-methyl-pyridine-2-carboxylic acid ethyl ester) and Pd(dppf) (461 mg, 0.565 mmol) in dioxane (250 mL). The mixture is stirred at 80° C. for 18 h before it is cooled to rt, diluted with ice-water (150 mL) and EA (250 mL) and acidified with 2 N aq. HCl. The org. layer is separated and the aq. phase is extracted with EA (3×100 mL) and DCM (4×100 mL). The aq. phase is neutralised by adding sat. aq. NaHCO3 solution and is again extracted with DCM (4×75 mL). The combined org. extracts are dried over MgSO4, filtered and concentrated. The crude product is purified by MPLC on silica gel eluting with a gradient of EA in heptane to give 5-ethyl-6-methyl-pyridine-2-carboxylic acid isopropyl ester (7.08 g) as a pale yellow oil; LC-MS: tR=0.77 min, [M+1]+=207.99. 1H NMR (CDCl3): δ 1.25 (t, J=7.5 Hz, 3H), 1.41 (d, J=6.3 Hz, 6H), 2.63 (s, 3H), 2.70 (q, J=7.5 Hz, 2H), 5.30 (hept, J=6.3 Hz, 1H), 7.54 (d, J=8.0 Hz, 1H), 7.87 (d, J=8.0 Hz, 1H).

Workup

  1. temperatureis cooled to rt
  2. customlayer is separated
  3. extractionthe aq. phase is extracted with EA (3×100 mL) and DCM (4×100 mL)
  4. additionby adding sat. aq. NaHCO3 solution
  5. extractionis again extracted with DCM (4×75 mL)
  6. dry with materialextracts are dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product is purified by MPLC on silica gel eluting with a gradient of EA in heptane

Sources & evidence

ORD record
ord-bf8226b738c94d39b829a2fe9e7ac197
Source dataset
uspto-grants-2013_12
Patent number
US08598208B2

Reaction notes

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