Formamide → Tert-butyl 4-(2-carbamoylbenzofuran-5-yl)piperazine-1-carboxylate

HRID 1883955

반응식

HRID 1883955 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[CH:16][C:17]([OH:22])=[C:18]([CH:21]=2)C=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:30][C:31](OCC)=O.[CH:36]([NH2:38])=[O:37].C[O-].[Na+]>C(OCC)(=O)C.O.CN1C(=O)CCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[CH:16][C:17]3[O:22][C:31]([C:36]([NH2:38])=[O:37])=[CH:30][C:18]=3[CH:21]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

참가 물질

9

반응물 5

HCID 713FormamideHCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 10942334Sodium MethoxideHCID 23508726tert-Butyl 4-(3-formyl-4-hydroxyphenyl)piperazine-1-carboxylate

생성물 1

HCID 11244883Tert-butyl 4-(2-carbamoylbenzofuran-5-yl)piperazine-1-carboxylate

시약·촉매·용매 3

HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

1.04 g of 5-(4-tert-butoxycarbonylpiperazin-1-yl)-2-hydroxybenzaldehyde are added at 20° under nitrogen with stirring to 10 ml of NMP, and 0.5 g of potassium carbonate and 0.4 ml of ethyl bromoacetate are added to the solution. The mixture is stirred at 120° for 5 hours and cooled to 25°. 0.4 ml of formamide is then added to the mixture, and stirring is continued for 30 minutes. 1.9 ml of sodium methoxide (30% solution in methanol) are then added over the course of 15 minutes without cooling, and stirring is continued for a further hour at 25-30°. 30 ml of water and 30 ml of ethyl acetate are added to the batch, the phases are separated, and the aqueous phase is extracted with 30 ml of ethyl acetate. The combined organic phases are washed with 30 ml of water, and the solvent is removed under reduced pressure (1.1 g of orange crystal slurry). After crystallization using 20 ml of toluene, 500 mg of pale-beige crystals remain. The mother liquor is evaporated, and the oil which remains is dissolved in 10 ml of toluene. After 3 hours at 0°, further pale-beige crystals form (identical with the first crystals; 70 mg). The total yield (0.57 g) is 49%, m.p. 202-204°; MS 345 (M+), 289 (100%), 272, 244, 215, 203.

후처리

  1. additionare added to the solution
  2. temperaturecooled to 25°
  3. stirringstirring
  4. waitis continued for 30 minutes
  5. temperaturewithout cooling
  6. stirringstirring
  7. waitis continued for a further hour at 25-30°
  8. customthe phases are separated
  9. extractionthe aqueous phase is extracted with 30 ml of ethyl acetate
  10. washThe combined organic phases are washed with 30 ml of water
  11. customthe solvent is removed under reduced pressure (1.1 g of orange crystal slurry)
  12. customAfter crystallization
  13. customThe mother liquor is evaporated
  14. dissolutionthe oil which remains is dissolved in 10 ml of toluene
  15. waitAfter 3 hours at 0°
  16. customThe total yield (0.57 g)

출처 및 근거

ORD 기록
ord-a52f8ab5361444d68cd368b6b2f3cf8a
출처 데이터셋
uspto-grants-2004_07
특허 번호
US06762300B2

연결된 노트

불러오는 중…