3-Hydroxypyridine → 3-[3-Bromo-5-(4-methoxy-benzyloxy)-phenoxy]-pyridine

HRID 1784814노트

반응식

HRID 1784814 반응식
Br[C:2]1[CH:3]=[C:4]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[CH:5]=[C:6]([Br:8])[CH:7]=1.[OH:19][C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1.[H-].[Na+].[OH-].[NH4+]>N1C(C)=CC(C)=CC=1C.[Cu]=O.C(OCC)(=O)C>[Br:8][C:6]1[CH:7]=[C:2]([CH:3]=[C:4]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[CH:5]=1)[O:19][C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1

참가 물질

8

반응물 4

HCID 79713-HydroxypyridineHCID 14923Ammonium HydroxideHCID 24758Sodium hydrideHCID 252583101,3-Dibromo-5-[(4-methoxyphenyl)methoxy]benzene

생성물 1

HCID 509938663-[3-Bromo-5-(4-methoxy-benzyloxy)-phenoxy]-pyridine수율 25%

시약·촉매·용매 3

HCID 14829Copper oxide촉매HCID 79532,4,6-Trimethylpyridine용매HCID 8857Ethyl Acetate용매

반응 조건

온도
210 °C

실험 절차

A mixture of the 3,5-dibromo-1-p-methoxy-benzyloxybenzene (250 mg, 0.672 mmol) and 3-hydroxypyridine (128 mg, 1.34 mmol) and 96 mg (0.67 mmol) copper oxide in 3 mL of collidine was treated with sodium hydride (27 mg, 0.67 mmol) in a stirred tube. After 10 minutes to allow off-gassing, the tube was sealed and the reaction mixture was heated to 210° C. bath temperature overnight. It was then cooled and treated with ethyl acetate and aqueous ammonium hydroxide, and filtered through Celite®. The phases were separated, and the aqueous phase was extracted with additional ethyl acetate. The combined organics were washed with brine, dried over sodium sulfate and concentrated. The product was chromatographed (33% ethyl acetate/hexane) to give 66 mg of product 3-[3-bromo-5-(4-methoxy-benzyloxy)-phenoxy]-pyridine (25% yield). This material was converted to 3-(1H-indol-4-yl)-5-(pyridin-3-yloxy)-phenol as described in Example 35. 1H NMR (400 MHz, CD3OD): δ 11.22 (s, 1H), 9.77 (s, 1H), 8.43 (d, J=2.5 Hz, 1H), 8.36 (d, J=3.5 Hz, 1H), 7.53 (ddd, J=8.4, 2.7,1.3 Hz, 1H), 7.42 (dd, J=8.4, 4.7Hz, 1H), 7.36 (dd, J=5.4, 2.4Hz, 2H), 7.11 (t, J=7.7 Hz, 1H), 7.00 (d, J=7.0 Hz, 1H), 6.86 (s, 1H), 6.65 (s, 1H), 6.45 (s, 1H), 6.40 (t, J=2.0 Hz, 1H).

후처리

  1. customthe tube was sealed
  2. temperatureIt was then cooled
  3. filtrationfiltered through Celite®
  4. customThe phases were separated
  5. extractionthe aqueous phase was extracted with additional ethyl acetate
  6. washThe combined organics were washed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customThe product was chromatographed (33% ethyl acetate/hexane)

출처 및 근거

ORD 기록
ord-da44352d4d494044ba354295353557ff
출처 데이터셋
uspto-grants-2009_03
특허 번호
US07504401B2

반응 노트

불러오는 중…