Methanol → HCID 89514906, compound

HRID 527443Notes

Reaction equation

HRID 527443 reaction equation
O=[C:2]([CH2:8][CH3:9])[CH2:3][CH2:4][C:5]([OH:7])=[O:6].Cl.[F:11][C:12]1[CH:17]=[CH:16][C:15]([NH:18]N)=[CH:14][CH:13]=1.S(=O)(=O)(O)O.[CH3:25]O>>[F:11][C:12]1[CH:17]=[C:16]2[C:15](=[CH:14][CH:13]=1)[NH:18][C:2]([CH2:3][CH2:4][C:5]([O:7][CH3:25])=[O:6])=[C:8]2[CH3:9]

Participants

5

Reactant 4

HCID 887MethanolHCID 1118Sulfuric AcidHCID 699814-Fluorophenylhydrazine hydrochlorideHCID 37997744-Oxohexanoic acid

Product 1

HCID 89514906HCID 89514906, compoundYield 46%

Conditions

Temperature
120 °C

Procedure

A stirred mixture of 88.8 mg (0.68 mmol) of 4-oxohexanoic acid,* 100 mg (0.62 mmol) of (4-fluorophenyl)hydrazine hydrochloride, 3 mL of methanol and 80 μL of concentrated sulfuric acid in a 5 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 (4 mL). The organic compound was repeatedly extracted with dichloromethane (3×5 mL) and the combined organic phases were washed with brine (4 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 46% yield (67 mg) as viscous mass. C13H14FNO2, Mr=235.25; 1H NMR (400 MHz, DMSO-d6) d: 2.12 (s, 3H), 2.66 (t, J=8.0 Hz, 2H), 2.93 (t, J=7.6 Hz, 2H), 3.58 (s, 3H), 6.80 (td, J=2.8/9.2 Hz, 1H), 7.10 (dd, J=2.4/10.2 Hz, 1H), 7.20 (dd, J=4.6/8.6 Hz, 1H), 10.74 (bs, 1H); 19F NMR (282 MHz, DMSO-d6) d: −124.03 (d, 5′-F); LCMS (ESI) tR: 2.58 min (>99%, UV220), m/z: 236.2 [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 (4 mL)
  4. extractionThe organic compound was repeatedly extracted with dichloromethane (3×5 mL)
  5. washthe combined organic phases were washed with brine (4 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-455aa0de26f7493aa0b05876c7274191
Source dataset
uspto-grants-2016_05
Patent number
US09346803B2

Reaction notes

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