Ethyl bromoacetate → Ethyl 3-(4-chlorophenyl)-2-indolin-N-ylpropanoate

HRID 30382

반응식

HRID 30382 반응식
O[Li].O.[NH:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6][CH2:5]1.Br[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16].[Cl:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25]Br)=[CH:23][CH:22]=1>CN(C=O)C>[Cl:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25][CH:14]([N:4]2[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[CH2:6][CH2:5]2)[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:23][CH:22]=1

참가 물질

6

반응물 4

HCID 7748Ethyl bromoacetateHCID 10328IndolineHCID 693291-(Bromomethyl)-4-chlorobenzeneHCID 168937Lithium hydroxide, monohydrate

생성물 1

HCID 22270659Ethyl 3-(4-chlorophenyl)-2-indolin-N-ylpropanoate

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
-78 °C

실험 절차

In an oven-dried flask under an atmosphere of nitrogen, 1.1 g LiOH.H2O (26.25 mmol) in DMF (20 mL) was added to a stirring suspension of 4 angstrom molecular sieves. After 30 minutes of stirring at room temperature 2.8 mL (25 mmol) indoline was added dropwise. After one hour at room temperature 2.9 mL (26.25 mmol) Ethyl bromoacetate was added dropwise. After 1.5 h the solid material was filtered and the residue was washed with copious amounts of EtOAc. The organics were washed 3 times with water and the organic material was dried over MgSO4. The solvents were evaporated under reduced pressure. The crude material was then dissolved in 75 mL anhydrous THF, charged into an oven dried round bottom under an atmosphere of nitrogen, cooled to −78° C., and then treated with 26.25 mL a 1M solution of NaHMDS. The solution was allowed to stir for 30 minutes at −78° C. after which the enolate was quenched with 5.4 g (26.25 mmol) of parachlorobenzyl bromide (solution in 25 mL anhydrous THF). The reaction was allowed to warm to room temperature overnight. The next day the reaction was quenched with water. The aqueous layer was extracted with 3 large portions of EtOAc. The combined organics were dried over MgSO4. The solvents were removed under reduced pressure and the residue was purified by flash chromatography which yielded the title compound as a yellow oil. LC/MS m/e=331 (M+1). TLC Rf=0.22 (20:1 hexanes:EtOAc). 1H NMR (500 MHz, CDCl3): δ 1.11 (t, J=3.55 Hz, 3H), 2.96 (m, 2H), 3.06 (m, 1H), 3.25 (m, 1H), 3.60 (t, 2H), 4.07 (m, 2H), 4.36 (t, J=3.75 Hz, 1H).

후처리

  1. additionwas added dropwise
  2. filtrationAfter 1.5 h the solid material was filtered
  3. washthe residue was washed with copious amounts of EtOAc
  4. washThe organics were washed 3 times with water
  5. dry with materialthe organic material was dried over MgSO4
  6. customThe solvents were evaporated under reduced pressure
  7. dissolutionThe crude material was then dissolved in 75 mL anhydrous THF
  8. additioncharged into an oven
  9. customdried round bottom under an atmosphere of nitrogen
  10. additiontreated with 26.25 mL a 1M solution of NaHMDS
  11. temperatureto warm to room temperature overnight
  12. customThe next day the reaction was quenched with water
  13. extractionThe aqueous layer was extracted with 3 large portions of EtOAc
  14. dry with materialThe combined organics were dried over MgSO4
  15. customThe solvents were removed under reduced pressure
  16. customthe residue was purified by flash chromatography which

출처 및 근거

ORD 기록
ord-2756bb44d6a24e17b666bb2106cbc880
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07423067B2

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