Sodium Carbonate → 5-(1-Isopropyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-carbaldehyde

HRID 1497477Notes

Reaction equation

HRID 1497477 reaction equation
I[C:2]1[CH:3]=[CH:4][C:5](=[O:11])[N:6]([CH:8]([CH3:10])[CH3:9])[CH:7]=1.[CH:12]([C:14]1[S:18][C:17](B(O)O)=[CH:16][CH:15]=1)=[O:13].C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:8]([N:6]1[C:5](=[O:11])[CH:4]=[CH:3][C:2]([C:17]2[S:18][C:14]([CH:12]=[O:13])=[CH:15][CH:16]=2)=[CH:7]1)([CH3:10])[CH3:9]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27734305-Formyl-2-thiopheneboronic acidHCID 595418575-iodo-1-isopropylpyridin-2(1H)-one

Product 1

HCID 866806355-(1-Isopropyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-carbaldehydeYield 53.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 5-iodo-1-isopropylpyridin-2(1H)-one (0.41 g, 1.55 mmol) in toluene (5 mL) and ethanol (2 mL) was added 5-formylthiophen-2-yl boronic acid (0.289 g, 1.87 mmol), 2M Na2CO3 (0.495 g, 4.67 mmol), and Pd(PPh3)4 (0.09 g, 0.07 mmol). The mixture was purged with argon and heated at 100° C. for about 2 h. The mixture was concentrated, diluted with water (50 mL), and extracted with ethyl acetate (2×200 mL). The combined organic extracts were washed with brine solution (20 mL), dried over Na2SO4 and concentrated under vacuum to obtain crude product. The crude product was purified by flash chromatography (silica gel, 60-120μ) using 20% ethyl acetate in hexane as eluent to afford 5-(1-isopropyl-6-oxo-1,6-dihydropyridin-3-yl)thiophene-2-carbaldehyde as an off-white solid (0.205 g, 53.3% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.18 (s, 1H), 7.99 (d, 1H), 7.78 (d, 1H), 7.62 (d, 1H), 7.58 (d, 1H), 7.53 (d, 1H), 5.08-5.01 (m, 1H), 1.21 (t, 6H), LC-MS m/z calcd for [M+H]+ 248.07. found 248.1.

Workup

  1. customThe mixture was purged with argon
  2. concentrationThe mixture was concentrated
  3. additiondiluted with water (50 mL)
  4. extractionextracted with ethyl acetate (2×200 mL)
  5. washThe combined organic extracts were washed with brine solution (20 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under vacuum
  8. customto obtain crude product
  9. customThe crude product was purified by flash chromatography (silica gel, 60-120μ)

Sources & evidence

ORD record
ord-9c874faa0f8f4d088ca89cee9841679f
Source dataset
uspto-grants-2015_12
Patent number
US09199975B2

Reaction notes

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