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Potassium Carbonate → (3-{3-[(2,2-Diphenyl-ethyl)-(2-fluoro-3-trifluoromethyl-benzyl)-amino]-propoxy}-phenyl)-acetic acid methyl ester

HRID 881656
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HRID 881656 반응식
[CH3:1][O:2][C:3](=[O:30])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH2:14][NH:15][CH2:16][CH:17]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:6]=1.[F:31][C:32]1[C:39]([C:40]([F:43])([F:42])[F:41])=[CH:38][CH:37]=[CH:36][C:33]=1[CH2:34]Br.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[CH3:1][O:2][C:3](=[O:30])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH2:14][N:15]([CH2:16][CH:17]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:34][C:33]2[CH:36]=[CH:37][CH:38]=[C:39]([C:40]([F:41])([F:43])[F:42])[C:32]=2[F:31])[CH:6]=1
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HCID 11430Potassium CarbonateHCID 27375691-(Bromomethyl)-2-fluoro-3-(trifluoromethyl)benzeneHCID 68906807{3-[3-(2,2-Diphenyl-ethylamino)-propoxy]-phenyl}-acetic acid methyl ester

생성물 1

HCID 68914106(3-{3-[(2,2-Diphenyl-ethyl)-(2-fluoro-3-trifluoromethyl-benzyl)-amino]-propoxy}-phenyl)-acetic acid methyl ester수율 72.5%

시약·촉매·용매 2

HCID 962
Water
용매
HCID 6228Dimethylformamide용매

반응 조건

온도
45 °C

실험 절차

To a solution of {3-[3-(2,2-diphenyl-ethylamino)-propoxy]-phenyl}-acetic acid methyl ester (3) (0.7 g, 0.002 mol) in DMF (10 mL), was added 2-fluoro-3-(trifluoromethyl)benzyl bromide (0.5 g, 0.002 mol) and powdered potassium carbonate (1.93 g, 0.014 mol), the reaction mixture was heated and stirred at 45° C. for 18 hours. After cooling, the reaction mixture was diluted with water (30 mL) and extracted with EtOAc (3×25 mL). The combined organic extracts were washed with brine (15 mL), dried over Na2SO4, concentrated to an oil, which was purified by flash chromatography (8:2 Hexanes/EtOAc) to give the desired product as oil 0.84 g in 72% yield. 1H NMR (CDCl3) δ 7.35 (t, 1H), 7.17 (m, 12H), 6.85 (t, 2H), 6.63 (s, 1H), 6.59 (t, 1H), 4.16 (t, 1H), 3.69 (s, 3H), 3.68 (s, 2H), 3.63 (t, 2H), 3.57 (d, 2H), 3.10 (d, 2H), 2.67 (t, 2H), 1.82 (t, 2H). 13C NMR (CDCl3) δ 173.4, 160.4, 144.8, 136.6, 130.8, 130.8, 129.7, 129.6, 129.4, 127.7, 126.8, 124.9, 123.1, 122.8, 116.8, 114.5, 66.3, 61.4, 53.5, 52.4, 51.8, 51.1, 42.7, 28.3.

후처리

  1. temperaturethe reaction mixture was heated
  2. temperatureAfter cooling
  3. extractionextracted with EtOAc (3×25 mL)
  4. washThe combined organic extracts were washed with brine (15 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to an oil, which
  7. customwas purified by flash chromatography (8:2 Hexanes/EtOAc)

출처 및 근거

ORD 기록
ord-acac523b55744e2f97711f9755e98f61
출처 데이터셋
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08993628B2

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