Diethylamine → tert-butyl N-[(3S)-1-methyl-2-oxo-3-[3-[4-[3-(trifluoromethoxy)phenyl]-2-pyridyl]prop-2-ynyl]pyrrolidin-3-yl]carbamate

HRID 624302노트

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HRID 624302 반응식
[CH3:1][N:2]1[CH2:6][CH2:5][C@@:4]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])([CH2:7][C:8]#[CH:9])[C:3]1=[O:18].I[C:20]1[CH:25]=[C:24]([C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([O:32][C:33]([F:36])([F:35])[F:34])[CH:27]=2)[CH:23]=[CH:22][N:21]=1.N(CC)CC>C1COCC1.[Cu](I)I.[Cu]I>[CH3:1][N:2]1[CH2:6][CH2:5][C@@:4]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:15])([CH3:14])[CH3:16])([CH2:7][C:8]#[C:9][C:20]2[CH:25]=[C:24]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([O:32][C:33]([F:34])([F:35])[F:36])[CH:27]=3)[CH:23]=[CH:22][N:21]=2)[C:3]1=[O:18]

참가 물질

7

반응물 3

HCID 8021DiethylamineHCID 89649283tert-Butyl N-[(3S)-1-methyl-2-oxo-3-prop-2-ynyl-pyrrolidin-3-yl]carbamateHCID 896493782-Iodo-4-[3-(trifluoromethoxy)phenyl]pyridine

생성물 1

HCID 89649351tert-butyl N-[(3S)-1-methyl-2-oxo-3-[3-[4-[3-(trifluoromethoxy)phenyl]-2-pyridyl]prop-2-ynyl]pyrrolidin-3-yl]carbamate수율 99.8%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 83717Copper iodide촉매HCID 8028Tetrahydrofuran용매

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온도
20 °C

실험 절차

Copper Iodide (104.92 mg, 0.5500 mmol), followed by PdCl2(Ph3P)2 (193.34 mg, 0.2800 mmol) was added portionwise to a solution of the tert-butyl N-[(3S)-1-methyl-2-oxo-3-prop-2-ynyl-pyrrolidin-3-yl]carbamate (2.78 g, 11.02 mmol) (which may be prepared as described in Description 8), 2-iodo-4-[3-(trifluoromethoxy)-phenyl]pyridine (6.03 g, 16.53 mmol) (which may be prepared as described in Description 9) and Et2NH (5.7 mL, 55.09 mmol) in THF (60 mL) under N2 and the reaction was stirred at 20° C. for 18 hrs. Additional PdCl2(Ph3P)2 (1.25 mol %) and CuI (2.5 mol %) catalyst was added. The reaction was left to stir for 3 days. The solvent was evaporated and the residue was suspended in EtOAc and washed with water/sat. aq. NaHCO3. The organics were collected, dried (Na2SO4) and the solvent evaporated to afford a brown oil. This was purified using a Biotage SP4, with 100 g SNAP cartridge, eluting with 0 to 100% EtOAc in i-hexane. Clean fractions were collected and the solvent evaporated to afford a yellow oil. The remaining fractions were collected and re-columned using a SP4, 100 g SNAP cartridge, 0 to 10% MeOH/EtOAc and the product was collected and combined with the clean material from the first column to afford the tert-butyl N-[(3S)-1-methyl-2-oxo-3-[3-[4-[3-(trifluoromethoxy)phenyl]-2-pyridyl]prop-2-ynyl]pyrrolidin-3-yl]carbamate (D10) (5.38 g, 10.991 mmol, 99.8% yield) as a yellow oil containing some Ph3P residues;

후처리

  1. waitThe reaction was left
  2. stirringto stir for 3 days
  3. customThe solvent was evaporated
  4. washwashed with water/
  5. customThe organics were collected
  6. dry with materialdried (Na2SO4)
  7. customthe solvent evaporated
  8. customto afford a brown oil
  9. customThis was purified
  10. washwith 100 g SNAP cartridge, eluting with 0 to 100% EtOAc in i-hexane
  11. customwere collected
  12. customthe solvent evaporated
  13. customto afford a yellow oil
  14. customThe remaining fractions were collected
  15. customthe product was collected

출처 및 근거

ORD 기록
ord-b79b4cceccfb420090a9c4e07fe786ab
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09303032B2

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