Hydrochloric Acid → HCID 57808404, compound

HRID 1908710Notes

Reaction equation

HRID 1908710 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]([OH:10])=[O:9])[CH:5]=[CH:4][N:3]=1.Cl>O1CCOCC1.C1COCC1.CC(=O)OCC.O>[CH2:5]([C:2]1[CH:7]=[C:6]([CH:5]=[CH:4][N:3]=1)[C:8]([OH:10])=[O:9])[CH:6]([CH3:8])[CH3:7]

Participants

7

Reactant 2

HCID 313Hydrochloric AcidHCID 2369852-Chloroisonicotinic acid

Product 1

HCID 57808404HCID 57808404, compoundYield 137.8%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 2-chloro-pyridine-4-carboxylic acid (2.55 g, 16.2 mmol) in dioxane (50 mL), Pd(dppf) (132 mg, 0.162 mmol) is added. The mixture is stirred under argon at rt and isobutyl zinbromide (6.55 g, 32.4 mmol, 65 mL of a 0.5 M solution in THF) is added dropwise. The mixture is stirred at rt for 1 h, then at 100° C. for 16 h. The mixture is cooled to rt and diluted with EA (250 mL) and cold water (0° C.). The mixture is acidified by adding aq. 25% HCl. The org. phase is separated and the aq. phase is extracted with EA (4×50 mL) followed by DCM (6×50 mL). The combined org. extracts are concentrated and dried. The crude product is purified by MPLC on silica gel to give the title compound (2.0 g) in form of a pale yellow oil. LC-MS: tR=0.47 min, [M+1]+=180.09. 1H NMR (CD3OD): δ 1.03 (d, J=6.8 Hz, 6H), 2.12-2.24 (m, 1H), 3.00 (d, J=7.3 Hz, 2H), 8.29 (dd, J=5.8, 1.5 Hz, 1H), 8.34 (s, 1H), 8.88 (d, J=5.8 Hz, 1H).

Workup

  1. stirringThe mixture is stirred at rt for 1 h
  2. temperatureThe mixture is cooled to rt
  3. customphase is separated
  4. extractionthe aq. phase is extracted with EA (4×50 mL)
  5. concentrationextracts are concentrated
  6. customdried
  7. customThe crude product is purified by MPLC on silica gel

Sources & evidence

ORD record
ord-7730ec774c8949ad829287e773d276c6
Source dataset
uspto-grants-2013_12
Patent number
US08598208B2

Reaction notes

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