Methanol → HCID 68474536, compound

HRID 527442Notes

Reaction equation

HRID 527442 reaction equation
O=[C:2]([CH3:8])[CH2:3][CH2:4][C:5]([OH:7])=[O:6].Cl.[F:10][C:11]1[CH:16]=[CH:15][C:14]([NH:17]N)=[CH:13][CH:12]=1.S(=O)(=O)(O)O.[CH3:24]O>>[F:10][C:11]1[CH:16]=[C:15]2[C:14](=[CH:13][CH:12]=1)[NH:17][C:2]([CH3:8])=[C:3]2[CH2:4][C:5]([O:7][CH3:24])=[O:6]

Participants

5

Reactant 4

HCID 887MethanolHCID 1118Sulfuric AcidHCID 11579Levulinic AcidHCID 699814-Fluorophenylhydrazine hydrochloride

Product 1

HCID 68474536HCID 68474536, compoundYield 84%

Conditions

Temperature
120 °C

Procedure

A stirred mixture of 39.3 mg (0.34 mmol) of 4-oxopentanoic acid,* 50 mg (0.31 mmol) of (4-fluorophenyl)hydrazine hydrochloride, 1 mL of methanol and 40 μL of concentrated sulfuric acid in a 2 mL microwave process vial was heated for 10 min at 120° C. under argon in a microwave synthesizer. The alcoholic solution was concentrated to about one-third of its original volume and then transferred to a phase separator syringe filled with cold water (2 mL). The organic compound was repeatedly extracted with dichloromethane (3×3 mL) and the combined organic phases were washed with brine (2 mL), dried over Na2SO4 and filtered. Removal of the organic solvent and treatment of the residue with a little hexane afford the title compound in 84% yield (39 mg) as viscous mass. C12H12FNO2, Mr=221.23; 1H NMR (400 MHz, DMSO-d6) d: 2.31 (s, 3H), 3.57 (s, 3H), 3.65 (s, 2H), 6.81 (td, J=2.4/9.2 Hz, 1H), 7.10 (dd, J=2.4/10.0 Hz, 1H), 7.21 (dd, J=4.4/8.8 Hz, 1H), 10.97 (s, 1H); 19F NMR (282 MHz, DMSO-d6) d: −123.78 (d, 5′-F); LCMS (ESI) tR: 2.18 min (95%, UV220, ELSD), m/z: 222.2 [M+1]+. [* instead of the acid one could also use the methyl ester with the same outcome]

Workup

  1. concentrationThe alcoholic solution was concentrated to about one-third of its original volume
  2. customtransferred to a phase separator syringe
  3. additionfilled with cold water (2 mL)
  4. extractionThe organic compound was repeatedly extracted with dichloromethane (3×3 mL)
  5. washthe combined organic phases were washed with brine (2 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customRemoval of the organic solvent and treatment of the residue with a little hexane

Sources & evidence

ORD record
ord-71348973f4114e298e383d31f8f8dc94
Source dataset
uspto-grants-2016_05
Patent number
US09346803B2

Reaction notes

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