N-Methoxy-N-methylacetamide → HCID 89781970, compound

HRID 1056056Notes

Reaction equation

HRID 1056056 reaction equation
[Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][C:6]([F:12])=[CH:7][CH:8]=2)[N:3]=1.[Li]CCCC.CON(C)[C:21](=[O:23])[CH3:22]>C1COCC1>[Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[C:5]([C:21](=[O:23])[CH3:22])[C:6]([F:12])=[CH:7][CH:8]=2)[N:3]=1

Participants

5

Reactant 3

HCID 537505N-Methoxy-N-methylacetamideHCID 537490892-Chloro-7-fluoroquinolineHCID 178418339Butyllithium

Product 1

HCID 89781970HCID 89781970, compoundYield 15.16%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 2-chloro-7-fluoroquinoline (ECA International Corp, Palatine, Ill.; 300 mg, 1.652 mmol) in THF (5.0 mL) at −78° C. was added nBuLi, 1.6 M in hexanes (1.24 mL, 1.98 mmol) slowly dropwise. The solution was stirred at −78° C. for 30 min. A solution of N-methoxy-N-methylacetamide (0.25 mL, 2.48 mmol) in THF (0.5 mL) was added slowly dropwise via syringe. After 10 min, the reaction was warmed to RT. After 15 min, the reaction was quenched by addition of saturated aq. NH4Cl. The reaction was partitioned between saturated NH4Cl and EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by silica gel chromatography, using 0-50% EtOAc/hexane. The pure fractions were combined and concentrated in vacuo to give 1-(2-chloro-7-fluoroquinolin-8-yl)ethanone (56 mg, 0.250 mmol, 15.16% yield): 1H NMR (400 MHz, DMSO-d6) δ ppm 8.57 (d, J=8.6 Hz, 1H), 8.25 (dd, J=9.1, 6.2 Hz, 1H), 7.65-7.74 (m, 2H), 2.68 (s, 3H). m/z (ESI, +ve ion) 224.0 (M+H)+.

Workup

  1. waitAfter 10 min
  2. temperaturethe reaction was warmed to RT
  3. waitAfter 15 min
  4. customthe reaction was quenched by addition of saturated aq. NH4Cl
  5. customThe reaction was partitioned between saturated NH4Cl and EtOAc
  6. washThe organic layer was washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude material was purified by silica gel chromatography
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-42d5bc81069145438dbcdec3abb7668f
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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