Hydrochloric Acid → HCID 57249145, compound

HRID 1857485Notes

Reaction equation

HRID 1857485 reaction equation
C[O:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:13]([F:16])([F:15])[F:14])[CH:11]=2)[N:6]=[CH:5][CH:4]=1.[CH3:17][Mg]Cl.Cl[C:21]([O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:22].Cl>O1CCCC1.CO>[CH2:24]([O:23][C:21]([N:6]1[C:7]2[C:12](=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][CH:8]=2)[C:3](=[O:2])[CH2:4][CH:5]1[CH3:17])=[O:22])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10387Benzyl chloroformateHCID 224611274-Methoxy-6-(trifluoromethyl)quinolineHCID 178418332HCID 178418332, compound

Product 1

HCID 57249145HCID 57249145, compoundYield 69%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

4-Methoxy-6-trifluoromethylquinoline (5.0 g, 22.0 mmol) was dissolved in anhydrous tetrahydrofuran (20 mL). The mixture was cooled to -78 ° C., and methyl magnesium chloride (73 mL of a 3.0M solution in tetrahydrofuran, 220 mmol) was added to the resulting slurry. After addition, benzyl chloroformate (41 mL, 286 mmol) was added to the slurry. After stirring at room temperature overnight, 75 mL of methanol was added followed by 75 mL of a 1N aqueous HCl solution. After hydrolysis of the intermediate enol ether was judged to be complete by thin layer chromatography, the volatiles were removed in vacuo, and the remaining aqueous phase was extracted with ethyl acetate (3×150 mL). The organic phases were combined and washed with a saturated sodium bicarbonate solution (2×75 mL), brine (100 mL), dried over sodium sulfate, filtered, and concentrated in vacuo to give 47 g of crude product. Purification by silica gel chromatography using 10% ethyl acetate/hexanes as eluent afforded 5.54 g of the title product (69%).1H NMR (CDCl3) δ 1.25 (d, 3H, J=7 Hz), 2.62 (dd, 1H, J=17, 2 Hz), 3.05 (dd, 1H, J=17, 6 Hz), 5.1-5.2 (m, 1H), 5.28 (d, 1H, J=12 Hz), 5.35 (d, 1H, J=12 Hz), 7.3-7.5 (m, 5H), 7.71 (dd, 1H, J=9,2 Hz), 8.05 (d, 1H, J=9 Hz), 8.27 (d, 1H, J=2 Hz).

Workup

  1. additionwas added to the slurry
  2. customthe volatiles were removed in vacuo
  3. extractionthe remaining aqueous phase was extracted with ethyl acetate (3×150 mL)
  4. washwashed with a saturated sodium bicarbonate solution (2×75 mL), brine (100 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give 47 g of crude product
  9. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-494e749e9d264bc397e5aeffe8627a1d
Source dataset
uspto-grants-2000_11
Patent number
US06147090

Reaction notes

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