Dichloromethane → HCID 66732183, compound

HRID 1963165Notes

Reaction equation

HRID 1963165 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[C:12]([C:16]1[S:20][C:19](B2OC(C)(C)C(C)(C)O2)=[CH:18][CH:17]=1)([CH3:15])([CH3:14])[CH3:13].C([O-])([O-])=O.[K+].[K+].C(Cl)Cl>CO.Cl[Pd]Cl.O>[C:12]([C:16]1[S:20][C:19]([C:2]2[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=2)[C:5]([O:7][CH3:8])=[O:6])=[CH:18][CH:17]=1)([CH3:15])([CH3:14])[CH3:13]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 2736842Methyl 2-chloropyridine-4-carboxylateHCID 665200471251848-80-2

Product 1

HCID 66732183HCID 66732183, compoundYield 76%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

Methyl 2-chloroisonicotinate (175 mg, 1.02 mmol), 2-(5-tert-butylthiophen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (300 mg, 1.13 mmol), K2CO3 (85 mg, 0.61 mmol) and PdCl2 (dppf) (37.3 mg, 0.05 mmol) was stirred in methanol (2 mL) and heated in a single node microwave reactor to 100° C. for 30 min. DCM (50 mL) and water (50 mL) were added, shaken and the phases separated. The aqueous phase was extracted with DCM (50 mL). The combined organic phases were dried with a phase separator and evaporated in vacuo. The residue was purified by automated flash chromatography on a Biotage® KP-SIL 50 g column. A gradient from 5% EtOAc in heptane over 2 CV followed by 5% to 20% of EtOAc in heptane over 9 CV was used as mobile phase. The product was collected using the wavelength 295 nm. The product fractions were collected and evaporated in vacuo yielding methyl 2-(5-tert-butylthiophen-2-yl)isonicotinate (213 mg, 76%). 1H NMR (600 MHz, cdcl3) δ 1.41 (s, 9H), 3.96 (s, 3H), 6.85 (d, 1H), 7.50 (s, 1H), 7.61 (d, 1H), 8.13 (s, 1H), 8.64 (d, 1H). MS m/z 276 (M+H)+

Workup

  1. customthe phases separated
  2. extractionThe aqueous phase was extracted with DCM (50 mL)
  3. customThe combined organic phases were dried with a phase separator
  4. customevaporated in vacuo
  5. customThe residue was purified by automated flash chromatography on a Biotage® KP-SIL 50 g column
  6. customThe product was collected
  7. customThe product fractions were collected
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-7f31785d08d44aafae73b627a61f79c3
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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