Hydrochloric Acid → N-(2-Chloro-4-formyl-5-methoxyphenyl)acrylamide

HRID 1897567노트

반응식

HRID 1897567 반응식
[C:1]([OH:5])(=O)[CH:2]=[CH2:3].[NH2:6][C:7]1[C:14]([Cl:15])=[CH:13][C:10]([CH:11]=[O:12])=[C:9]([O:16][CH3:17])[CH:8]=1.C(N(CC)CC)C.Cl>C(OCC)(=O)C.O>[Cl:15][C:14]1[CH:13]=[C:10]([CH:11]=[O:12])[C:9]([O:16][CH3:17])=[CH:8][C:7]=1[NH:6][C:1](=[O:5])[CH:2]=[CH2:3]

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 6581Acrylic AcidHCID 8471TriethylamineHCID 536468194-Amino-5-chloro-2-methoxybenzaldehyde

생성물 1

HCID 49779272N-(2-Chloro-4-formyl-5-methoxyphenyl)acrylamide수율 71%

시약·촉매·용매 2

HCID 962Water용매HCID 8857Ethyl Acetate용매

반응 조건

온도
35 °C

실험 절차

Acrylic acid (commercially available, for example, from Aldrich) (46 ml, 0.67 mol) was added slowly to a stirred suspension of 4-amino-5-chloro-2-methoxybenzaldehyde (Step B) (50.0 g, 0.27 mol) and triethylamine (204 g, 2.02 mol) in ethyl acetate (0.85 L) at 25° C. Propanephosphonic anhydride (50% in ethyl acetate; 429 g, 0.67 mol) was added over 30 minutes keeping reaction temperature at 30-40° C. The mixture was stirred at 30-40° C. for a further 1 hour and then cooled to 25° C. and diluted with water (0.26 L) and acidified with 32% hydrochloric acid (108 g) to pH 2-3. The organic layer was separated and washed with a mixture of water (0.23 L) and 32% sodium hydroxide (14 g)—aqueous layer ca. pH 7. The organic phase was washed with water (0.23 L) and then concentrated under reduced pressure (ca. 300 mbar) to remove 0.56 kg of distillate. Methylcyclohexane (335 g) was added and then a further 286 g of distillate was removed under reduced pressure. Methylcyclohexane (111 g) was added and then the resulting suspension was cooled to 20° C., filtered and washed with methylcyclohexane. The cake was dried at 40° C. under reduced pressure for 12 hours to give N-[2-chloro-4-formyl-5-(methyloxy)phenyl]-2-propenamide (46 g, 71%)

후처리

  1. customreaction temperature at 30-40° C
  2. temperaturecooled to 25° C.
  3. customThe organic layer was separated
  4. washwashed with a mixture of water (0.23 L) and 32% sodium hydroxide (14 g)—aqueous layer
  5. washThe organic phase was washed with water (0.23 L)
  6. concentrationconcentrated under reduced pressure (ca. 300 mbar)
  7. customto remove 0.56 kg of distillate
  8. additionMethylcyclohexane (335 g) was added
  9. customa further 286 g of distillate was removed under reduced pressure
  10. additionMethylcyclohexane (111 g) was added
  11. temperaturethe resulting suspension was cooled to 20° C.
  12. filtrationfiltered
  13. washwashed with methylcyclohexane
  14. customThe cake was dried at 40° C. under reduced pressure for 12 hours

출처 및 근거

ORD 기록
ord-c858f3299d9f445e9bea3a8675c37afb
출처 데이터셋
uspto-grants-2013_08
특허 번호
US08519138B2

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