5-Bromosalicylic acid → 3'-Chloro-4'-fluoro-4-hydroxy-biphenyl-3-carboxylic acid

HRID 2373782노트

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HRID 2373782 반응식
[Cl:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][C:7]=1[F:8].Br[C:13]1[CH:14]=[CH:15][C:16]([OH:22])=[C:17]([CH:21]=1)[C:18]([OH:20])=[O:19].C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([C:13]2[CH:14]=[CH:15][C:16]([OH:22])=[C:17]([C:18]([OH:20])=[O:19])[CH:21]=2)[CH:5]=[CH:6][C:7]=1[F:8]

참가 물질

6

반응물 3

HCID 69725-Bromosalicylic acidHCID 10340Sodium CarbonateHCID 27346603-Chloro-4-fluorophenylboronic Acid (contains varying amounts of Anhydride)

생성물 1

HCID 219213173'-Chloro-4'-fluoro-4-hydroxy-biphenyl-3-carboxylic acid수율 43.8%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 80711,2-Dimethoxyethane용매

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온도
80 °C

실험 절차

3-Chloro-4-fluoro-phenylboronic acid (3.2 g, 18.4 mmol), 5-bromo-2-hydroxy-benzoic acid (4.0 g, 18.4 mmol), and Pd (PPh3)4 (1.67 g, 1.84 mmol) were dissolved in 250 mL of DME, a 1 M Na2CO3 solution (46 mL, 46.0 mmol) added and the mixture heated to 80° C. for 20 h. The reaction mixture was filtered, partially evaporated and EtOAc (200 mL) and 1 N HCl (100 mL) added. The organic layer washed with 1N HCl and saturated sodium bicarbonate, dried over sodium sulfate, and evaporated. The crude material was filtered through a silica plug (THF) to give 3′-chloro-4′-fluoro-4-hydroxy-biphenyl-3-carboxylic acid (2.15 g).

후처리

  1. filtrationThe reaction mixture was filtered
  2. custompartially evaporated
  3. additionEtOAc (200 mL) and 1 N HCl (100 mL) added
  4. washThe organic layer washed with 1N HCl and saturated sodium bicarbonate
  5. dry with materialdried over sodium sulfate
  6. customevaporated
  7. filtrationThe crude material was filtered through a silica plug (THF)

출처 및 근거

ORD 기록
ord-90c5c581e3844ef390a161f7f73dad68
출처 데이터셋
uspto-grants-2008_12
특허 번호
US07459472B2

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