Tetrahydrofuran → Methyl 3-(2-(((2-(1,1-dimethylethyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)-4-pyridinyl)propanoate

HRID 1662499

반응식

HRID 1662499 반응식
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[CH:18][C:17]=3[F:24])=[C:12]([C:25]([CH3:28])([CH3:27])[CH3:26])[CH:11]=2)[CH:3]=1.C1COCC1.[Br-].[CH2:35]([O:37][C:38](=[O:42])[CH2:39][CH2:40][Zn+])C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].CC(P(C(C)(C)C)[C]1[CH][CH][CH][CH]1)(C)C.C1C=CC([C]2[C](C3C=CC=CC=3)[C](C3C=CC=CC=3)[C](C3C=CC=CC=3)[C]2C2C=CC=CC=2)=CC=1.[Fe]>[CH3:26][C:25]([C:12]1[CH:11]=[C:10]([CH2:9][O:8][C:4]2[CH:3]=[C:2]([CH2:40][CH2:39][C:38]([O:37][CH3:35])=[O:42])[CH:7]=[CH:6][N:5]=2)[CH:15]=[CH:14][C:13]=1[C:16]1[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[CH:18][C:17]=1[F:24])([CH3:28])[CH3:27]

참가 물질

6

반응물 3

HCID 8028Tetrahydrofuran2회HCID 577066404-Bromo-2-(((2-(1,1-dimethylethyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)pyridineHCID 178471816HCID 178471816, 화합물

생성물 1

HCID 57706116Methyl 3-(2-(((2-(1,1-dimethylethyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)-4-pyridinyl)propanoate

시약·촉매·용매 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium촉매HCID 178454872HCID 178454872, 화합물촉매

반응 조건

온도
80 °C

실험 절차

To a sealed tube containing 72.2 (0.0980 g, 0.22 mmol), bis(dibenzylideneacetone)palladium (0.0068 g, 0.012 mmol), and CTC-Q-Phos (commercially available from Strem Chemicals.) (0.0083 g, 0.0116 mmol) was added dry THF (3.000 mL, 0.22 mmol). After about 5 minutes, 3-ethoxy-3-oxopropylzinc bromide, 0.5M solution in THF (1.000 mL, 0.50 mmol) was added dropwise. After 1 hour, the mixture was heated to 80° C. and monitored with TLC and LC-MS. After 16.5 hours, the reaction was cooled to room temperature and the organic solvent was then removed under reduced pressure. The residue was purified by flash chromatography (SiO2 gel 60, eluted with 0 to 40% EtOAc in hexanes). Fractions containing the desired product were combined and concentrated to a light brown oil (0.0646 g, 63%). 1H NMR (400 MHz) (CDCl3) δ ppm 8.11 (1H, d, J=5.3 Hz), 7.65 (1H, d, J=1.6 Hz), 7.32 (1H, dd, J=7.7, 1.7 Hz), 7.07 (2H, m), 6.85 (1H, dt, J=8.9, 3.6 Hz), 6.80 (2H, m), 6.70 (1H, s), 5.41 (2H, s), 4.15 (2H, q, J=7.2 Hz), 3.79 (3H, s), 2.93 (2H, t, J=7.6 Hz), 2.64 (2H, t, J=7.7 Hz), 1.29 (12H, m).

후처리

  1. waitAfter 1 hour
  2. waitAfter 16.5 hours
  3. temperaturethe reaction was cooled to room temperature
  4. customthe organic solvent was then removed under reduced pressure
  5. customThe residue was purified by flash chromatography (SiO2 gel 60, eluted with 0 to 40% EtOAc in hexanes)
  6. additionFractions containing the desired product
  7. concentrationconcentrated to a light brown oil (0.0646 g, 63%)

출처 및 근거

ORD 기록
ord-6cbc49d3e69d4d93badc8cdde1cbdb35
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08030354B2

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