Trifluoroacetic acid → tert-Butyl 4-(5-fluoro-6-nitro-1-oxoisoindolin-2-yl)piperidine-1-carboxylate

HRID 2093798

반응식

HRID 2093798 반응식
[F:1][C:2]1[C:23]([N+:24]([O-:26])=[O:25])=[CH:22][C:5]([C:6]([NH:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)=[O:7])=[C:4]([CH:27]=C)[CH:3]=1.O=[O+][O-].C(O)(C(F)(F)F)=O.C([SiH](CC)CC)C.C([O-])(O)=O.[Na+].CC(OC(OC(OC(C)(C)C)=O)=O)(C)C>C(Cl)Cl.O>[F:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:22][C:23]=1[N+:24]([O-:26])=[O:25])[C:6](=[O:7])[N:8]([CH:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:20])([CH3:19])[CH3:21])=[O:16])[CH2:11][CH2:10]1)[CH2:27]2

참가 물질

9

반응물 6

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 24823OzoneHCID 90495Di-tert-butyl dicarbonateHCID 516892Sodium BicarbonateHCID 86653322tert-Butyl 4-(4-fluoro-5-nitro-2-vinylbenzamido)piperidine-1-carboxylate

생성물 1

HCID 67168225tert-Butyl 4-(5-fluoro-6-nitro-1-oxoisoindolin-2-yl)piperidine-1-carboxylate

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매2회

실험 절차

tert-Butyl 4-(4-fluoro-5-nitro-2-vinylbenzamido)piperidine-1-carboxylate (Step 2, 1.1 g, 2.77 mmol) in 50 mL of DCM is chilled to −78° C. Ozone was passed through the solution until the starting material was consumed, and then nitrogen was passed through the solution for 5 min. The reaction mixture was warmed to room temperature. Triphenylphosphine-resin (2.77 g) in 10 mL of DCM was added, and was stirred for another 1.5 h. The resin was filtered off, and the solution was concentrated in vacuo. The resulting crude was dissolved in DCM (15 mL), and to this solution were added TFA (15 mL) and triethylsilane (1.0 mL, 5.9 mmol) sequentially. The reaction was stirred at room temperature 2 h. After concentration, the reaction crude was poured into 10 mL of water, neutralized to pH 8 with sat. aq. NaHCO3, followed by addition of (Boc)2O (603 mg, 2.77 mmol) in 10 mL of DCM. The reaction was stirred at room temperature for 1.5 h, then extracted with DCM. The organic extracts were dried (Na2SO4), concentrated in vacuo, and purified by silica gel chromatography (EtOAc/Hexanes:1/4) to give tert-Butyl 4-(5-fluoro-6-nitro-1-oxoisoindolin-2-yl)piperidine-1-carboxylate; ESMS m/z 380.2 (M+H+).

후처리

  1. customwas consumed
  2. additionTriphenylphosphine-resin (2.77 g) in 10 mL of DCM was added
  3. filtrationThe resin was filtered off
  4. concentrationthe solution was concentrated in vacuo
  5. dissolutionThe resulting crude was dissolved in DCM (15 mL)
  6. stirringThe reaction was stirred at room temperature 2 h
  7. concentrationAfter concentration
  8. customthe reaction crude
  9. stirringThe reaction was stirred at room temperature for 1.5 h
  10. extractionextracted with DCM
  11. dry with materialThe organic extracts were dried (Na2SO4)
  12. concentrationconcentrated in vacuo
  13. custompurified by silica gel chromatography (EtOAc/Hexanes:1/4)

출처 및 근거

ORD 기록
ord-dcaa506af7a243348581a590d4b208bd
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08445505B2

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