Hydrochloric Acid → 3,5-difluoro-4-formyl-N-methylbenzamide

HRID 41097ノート

反応式

HRID 41097 の反応式
[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([F:13])[C:10]=1[CH:11]=[O:12])[C:5](O)=[O:6].C(Cl)(=O)C(Cl)=O.[CH3:20][NH2:21].Cl>ClCCl.CN(C)C=O>[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([F:13])[C:10]=1[CH:11]=[O:12])[C:5]([NH:21][CH3:20])=[O:6]

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 6329MethylamineHCID 65578Oxalyl chlorideHCID 450736293,5-Difluoro-4-formylbenzoic acid

生成物 1

HCID 866735663,5-difluoro-4-formyl-N-methylbenzamide収率 80.2%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide触媒HCID 6344Dichloromethane溶媒

実験手順

To an ice-cold solution of 3,5-difluoro-4-formylbenzoic acid (120 g, 645 mmol) in dichloromethane (1.5 L) and N,N-dimethylformamide (2.0 g, 27 mmol) was added oxalyl chloride (90 g, 709 mmol) drop-wise at a rate that allowed the mixture to not exceed an internal temperature of 10° C. The resulting mixture was stirred at the same temperature for 0.5 hr, warmed to room temperature, and stirred for an additional 1.5 hr. The solution was then cooled to 0° C., and aqueous methylamine (40%, 168 mL, 1.94 mol) was added drop-wise at a rate that allowed the mixture to not exceed an internal temperature of 7° C. Afterward, the mixture was quenched with aqueous HCl (2M, 335 mL, 670 mmol) and warmed to room temperature. The organic layer was separated, washed with brine (500 mL), dried over MgSO4, filtered, and concentrated under vacuum. The resulting residual solid was taken in MTBE (500 mL), and the resulting mixture was heated to reflux for 0.5 hr, cooled to room temperature, and stirred for 18 hr. Afterward, the mixture was cooled to 0° C., filtered, rinsed with pentane, and dried under vacuum to form the title compound (103 g, 80%) as a solid. 1H NMR (300 MHz, CDCl3) δ ppm 3.03 (d, J=4.86 Hz, 3H), 6.37 (br s, 1H), 7.36-7.42 (m, 2H), 10.36 (s, 1H); MS m/z 200.06 [M+H]+ (ESI).

後処理

  1. customan internal temperature of 10° C
  2. stirringstirred for an additional 1.5 hr
  3. temperatureThe solution was then cooled to 0° C.
  4. customan internal temperature of 7° C
  5. temperaturewarmed to room temperature
  6. customThe organic layer was separated
  7. washwashed with brine (500 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated under vacuum
  11. temperaturethe resulting mixture was heated
  12. temperatureto reflux for 0.5 hr
  13. temperaturecooled to room temperature
  14. stirringstirred for 18 hr
  15. temperatureAfterward, the mixture was cooled to 0° C.
  16. filtrationfiltered
  17. washrinsed with pentane
  18. customdried under vacuum

出典と根拠

ORDレコード
ord-3338972982a84806a94caaad22eddd66
出典データセット
uspto-grants-2013_09
特許番号
US08530467B2

反応ノート

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