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

HRID 1784814ノート

反応式

HRID 1784814 の反応式
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

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 14829Copper oxide触媒HCID 79532,4,6-Trimethylpyridine溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
210 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-da44352d4d494044ba354295353557ff
出典データセット
uspto-grants-2009_03
特許番号
US07504401B2

反応ノート

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