Toluene → 5'-Bromo-2',6-difluoro-[1,1'-biphenyl]-2-ol

HRID 1400772노트

반응식

HRID 1400772 반응식
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([OH:8])[C:3]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+].C1(C)C=CC=CC=1.[Br:25][C:26]1[CH:31]=[CH:30][C:29]([F:32])=[C:28](I)[CH:27]=1>CO.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>[Br:25][C:26]1[CH:27]=[CH:28][C:29]([F:32])=[C:30]([C:3]2[C:4]([OH:8])=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])[CH:31]=1

참가 물질

7

반응물 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27827504-Bromo-1-fluoro-2-iodobenzeneHCID 532162802-Fluoro-6-hydroxyphenylboronic acid

생성물 1

HCID 867108255'-Bromo-2',6-difluoro-[1,1'-biphenyl]-2-ol수율 89%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 887Methanol용매

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온도
105 °C

실험 절차

(2-Fluoro-6-hydroxyphenyl)boronic acid (50 mg, 0.321 mmol, 1.0 equiv), Pd(PPh3)4 (37.1 mg, 0.032 mmol, 0.1 equiv) and aqueous Na2CO3 (2 M, 401 μl, 0.802 mmol, 2.5 equiv) were mixed with toluene (2 mL) in a sealed microwave tube. 4-Bromo-1-fluoro-2-iodobenzene (96 mg, 0.321 mmol, 1.0 equiv) in MeOH (1.00 mL) was added to the above mixture. The resulted mixture was heated at 105° C. overnight. TLC showed the starting material disappeared and a new spot was produced. The reaction was allowed to cool to ambient temperature and then loaded on 12 g ISCO column and purified by 30% EtOAc/hexane to afford 5′-bromo-2′,6-difluoro-[1,1′-biphenyl]-2-ol (81 mg, 89%). 1H NMR (400 MHz, CHLOROFORM-d) δ 7.54 (dd, J=6.3, 2.5 Hz, 1H), 7.48 (ddd, J=8.7, 4.5, 2.6 Hz, 1H), 7.21 (td, J=8.2, 6.7 Hz, 1H), 7.07 (t, J=8.9 Hz, 1H), 6.81 (d, J=8.3 Hz, 1H), 6.71 (t, J=8.8 Hz, 1H). LCMS (M+1)=286.1.

후처리

  1. customa new spot was produced
  2. temperatureto cool to ambient temperature
  3. custompurified by 30% EtOAc/hexane

출처 및 근거

ORD 기록
ord-e738820b20ae42f688c3f0b5e687080d
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08906929B2

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