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

HRID 1662499

反応式

HRID 1662499 の反応式
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]

参加物

6

反応物 3

HCID 8028Tetrahydrofuran2 回HCID 577066404-Bromo-2-(((2-(1,1-dimethylethyl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)pyridineHCID 178471816HCID 178471816、化合物

生成物 1

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

試薬・触媒・溶媒 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium触媒HCID 178454872HCID 178454872、化合物触媒

反応条件

温度
80 °C

実験手順

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).

後処理

  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%)

出典と根拠

ORDレコード
ord-6cbc49d3e69d4d93badc8cdde1cbdb35
出典データセット
uspto-grants-2011_10
特許番号
US08030354B2

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