Sodium Carbonate → 3-Fluoro[1,1'-biphenyl]-2-amine

HRID 2276730노트

반응식

HRID 2276730 반응식
C([O-])([O-])=O.[Na+].[Na+].[C:7]1(B(O)O)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.Br[C:17]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:18]=1[NH2:19].C([O-])=O.[NH4+]>O.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC#N.O>[F:24][C:20]1[CH:21]=[CH:22][CH:23]=[C:17]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:18]=1[NH2:19]

참가 물질

9

반응물 4

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 2723923Ammonium formateHCID 27829402-Bromo-6-fluoroaniline

생성물 1

HCID 463146263-Fluoro[1,1'-biphenyl]-2-amine

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 18373917Acetonitrile--water (1/1)용매

반응 조건

온도
50 °C

실험 절차

To a solution of Na2CO3 (1.116 g, 10.53 mmol) in water (15 ml) was added poly(ethylene glycol) 2000 (17 g, 5.26 mmol) followed by palladium(II) acetate (0.024 g, 0.105 mmol). The suspension was heated to 50° C. Once the mixture became clear, phenylboronic acid (0.963 g, 7.89 mmol) followed by 2-bromo-6-fluoroaniline (1 g, 5.26 mmol) were added and heated at 120° C. for 30 min. The mixture was cooled, diluted with EtOAc, washed with water, dried and concentrated. The crude material was purified by ISCO (24 g REDISEP® silica column, gradient elution, 0-15% ethyl acetate in hexanes) to give Preparation 5A (800 mg, 81%): LCMS: HPLC: RT=2.016 min (MeCN/H2O with HCOONH4, Ascentis Express C8 2.7 μm 5×2.1 mm, gradient=4 min, wavelength=220 nm); MS(ES): m/z=188 [M+H]+; 1H NMR (CDCl3) δ 7.43-7.48 (m, 4H), 7.35-7.40 (m, 1H), 6.97-7.02 (m, 1H), 6.92 (dt, J=7.6, 1.2 Hz, 1H), 6.71-6.77 (m, 1H), 3.82 (br s, 2H).

후처리

  1. additionwere added
  2. temperatureheated at 120° C. for 30 min
  3. temperatureThe mixture was cooled
  4. washwashed with water
  5. customdried
  6. concentrationconcentrated
  7. customThe crude material was purified by ISCO (24 g REDISEP® silica column, gradient elution, 0-15% ethyl acetate in hexanes)
  8. customto give

출처 및 근거

ORD 기록
ord-e8ef268d8c3941569d58a87e702ce06f
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09133126B2

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