4-Bromo-2-(((2-(5,5-dimethyl-1-cyclopenten-1-yl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)pyridine → Ethyl 3-(2-(((2-(5,5-dimethyl-1-cyclopenten-1-yl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)-4-pyridinyl)propanoate

HRID 1662575

반응식

HRID 1662575 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]3[C:29]([CH3:31])([CH3:30])[CH2:28][CH2:27][CH:26]=3)[CH:11]=2)[CH:3]=1.[Br-].[CH2:33]([O:35][C:36](=[O:40])[CH2:37][CH2:38][Zn+])[CH3:34]>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].C1COCC1>[CH3:30][C:29]1([CH3:31])[C:25]([C:12]2[CH:11]=[C:10]([CH2:9][O:8][C:4]3[CH:3]=[C:2]([CH2:38][CH2:37][C:36]([O:35][CH2:33][CH3:34])=[O:40])[CH:7]=[CH:6][N:5]=3)[CH:15]=[CH:14][C:13]=2[C:16]2[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[CH:18][C:17]=2[F:24])=[CH:26][CH2:27][CH2:28]1

참가 물질

6

반응물 2

HCID 577058284-Bromo-2-(((2-(5,5-dimethyl-1-cyclopenten-1-yl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)pyridineHCID 178471816HCID 178471816, 화합물

생성물 1

HCID 57706923Ethyl 3-(2-(((2-(5,5-dimethyl-1-cyclopenten-1-yl)-2'-fluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methyl)oxy)-4-pyridinyl)propanoate수율 78%

시약·촉매·용매 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium촉매HCID 178454872HCID 178454872, 화합물촉매HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
80 °C

실험 절차

To a sealed tube containing 95.A (0.1059 g, 0.22 mmol), bis(dibenzylideneacetone)palladium (0.0068 g, 0.012 mmol), and CTC-Q-Phos (commercially available from Strem Chemicals) (0.0079 g, 0.011 mmol) was added dry THF (2.1 mL). After 5 minutes, 3-ethoxy-3-oxopropylzinc bromide, 0.5 M solution in THF (0.9 mL, 0.45 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 then the organic solvent was removed under reduced pressure. The solid was filtered off, and the solvent was concentrated. The residue was purified by silica gel flash chromatography (0-40% EtOAc/hexane) to afford 95.B (86.2 mg, 78% yield). 1H NMR (500 MHz) (CDCl3) δ ppm 8.10 (1H, d, J=5.4 Hz), 7.41 (1H, dd, J=7.9, 1.8 Hz), 7.33 (2H, dd, J=4.6, 1.5 Hz), 6.98 (1H, m), 6.81 (3H, m), 6.70 (1H, s), 5.52 (1H, t, J=2.0 Hz), 5.42 (2H, s), 4.15 (2H, q, J=7.1 Hz), 3.76 (3H, s), 2.93 (2H, t, J=7.7 Hz), 2.66 (2H, m), 2.25 (2H, td, J=7.0, 2.4 Hz), 1.66 (2H, t, J=7.0 Hz), 1.25 (3H, t, J=7.1 Hz), 0.86 (6H, s).

후처리

  1. waitAfter 1 hour
  2. waitAfter 16.5 hours
  3. temperaturethe reaction was cooled to room temperature
  4. customthe organic solvent was removed under reduced pressure
  5. filtrationThe solid was filtered off
  6. concentrationthe solvent was concentrated
  7. customThe residue was purified by silica gel flash chromatography (0-40% EtOAc/hexane)

출처 및 근거

ORD 기록
ord-c13e7fedcd5e494f9192825e06edb868
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08030354B2

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