Acetone → (E)-4-(3-(6-methoxypyridin-2-yl)thiophen-2-yl)but-3-en-2-one

HRID 656575Notes

Reaction equation

HRID 656575 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[C:7]([C:9]2[CH:13]=[CH:12][S:11][C:10]=2[CH:14]=O)[CH:6]=[CH:5][CH:4]=1.[CH3:16][C:17]([CH3:19])=[O:18].[OH-].[Na+].Cl>O>[CH3:1][O:2][C:3]1[N:8]=[C:7]([C:9]2[CH:13]=[CH:12][S:11][C:10]=2/[CH:14]=[CH:16]/[C:17](=[O:18])[CH3:19])[CH:6]=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 180AcetoneHCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 579992833-(6-Methoxypyridin-2-yl)thiophene-2-carbaldehyde

Product 1

HCID 57999307(E)-4-(3-(6-methoxypyridin-2-yl)thiophen-2-yl)but-3-en-2-oneYield 67%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a 500 mL recovery flask was added 3-(6-methoxypyridin-2-yl)thiophene-2-carbaldehyde (30C, 6.2 g, 28.3 mmol, 1.0 eq.), acetone (16.6 mL, 226 mmol, 8.0 eq.), and H2O (130 mL). Upon cooling to 0° C. in an ice bath, aqueous NaOH (5N, 6.2 mL, 31.1 mmol, 1.1 eq.) was added. The reaction mixture was stirred overnight while warming to room temperature. LC/MS monitoring showed the reaction to be ˜60% complete, so additional aqueous NaOH (5N, 1 mL, 5.0 mmol, 0.18 eq.) was added. After stirring for an additional 6 h the reaction was complete by LC/MS. The reaction mixture was neutralized with 3N aqueous HCl to a pH ˜8. The mixture was extracted with EtOAc (3×100 mL). The organic phases were combined and washed with saturated aqueous NaCl (100 mL). The combined aqueous phases were extracted with EtOAc (100 mL). The organic phases were combined and dried over anhydrous Na2SO4, filtered, and concentrated to give a black solid. The residue was purified via flash chromatography (60% CH2Cl2/Hex to 100% CH2Cl2) to give a yellow solid 30D (4.8 g, 67%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.29 (s, 3H) 3.96 (s, 3H) 6.59 (d, J=15.92 Hz, 1H) 6.84 (d, J=8.34 Hz, 1H) 7.41 (d, J=7.58 Hz, 1H) 7.60 (d, J=5.31 Hz, 1H) 7.75-7.88 (m, 2H) 8.71 (d, J=15.92 Hz, 1H). ESI-MS: m/z 260.3 (M+H)+.

Workup

  1. temperaturewhile warming to room temperature
  2. customthe reaction
  3. stirringAfter stirring for an additional 6 h the reaction
  4. extractionThe mixture was extracted with EtOAc (3×100 mL)
  5. washwashed with saturated aqueous NaCl (100 mL)
  6. extractionThe combined aqueous phases were extracted with EtOAc (100 mL)
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give a black solid
  11. customThe residue was purified via flash chromatography (60% CH2Cl2/Hex to 100% CH2Cl2)

Sources & evidence

ORD record
ord-bf523259d6be4d4495177ce22d4c97df
Source dataset
uspto-grants-2011_12
Patent number
US08071766B2

Reaction notes

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