Cesium carbonate → 4-(3-Fluorobenzylamino)benzonitrile

HRID 73144

反応式

HRID 73144 の反応式
C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Br[C:48]1[CH:55]=[CH:54][C:51]([C:52]#[N:53])=[CH:50][CH:49]=1.[F:56][C:57]1[CH:58]=[C:59]([CH:62]=[CH:63][CH:64]=1)[CH2:60][NH2:61].C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:56][C:57]1[CH:58]=[C:59]([CH:62]=[CH:63][CH:64]=1)[CH2:60][NH:61][C:48]1[CH:55]=[CH:54][C:51]([C:52]#[N:53])=[CH:50][CH:49]=1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 12162Benzonitrile, 4-bromo-HCID 668533-FluorobenzylamineHCID 634876Binap, (A+-)-

生成物 1

HCID 284758784-(3-Fluorobenzylamino)benzonitrile収率 79.9%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

In a flame-dried Schlenk tube, Pd(OAc)2 (304 mg, 1.3 mmol), Binap (1.69 g, 2.7 mmol), and 4-bromobenzonitrile (5.00 g, 27.1 mmol) were added under Ar to a stirring solution of 3-fluorobenzylamine (3.80 g, 30.4 mmol) and Cs2CO3 (13.20 g, 40.6 mmol) in dioxane (55 mL). The mixture was stirred at 80° C. (16 h) and then the volatiles were evaporated. CH2Cl2 (100 mL) and H2O (100 mL) were added and the layers separated. The aqueous layer was washed with CH2Cl2 (2×100 mL). The organic layers were combined, dried and concentrated under vacuum. The crude residue was purified by column chromatography (SiO2; EtOAc/hexanes 0/10 to 3/7) to obtain 4.90 g (78%) of a yellow solid: Rf=0.36 (1/9 EtOAc/hexanes); mp 63-64° C.; IR (nujol mull) 2934, 2861, 2214, 1739, 1605, 1527, 1457, 1375, 1285, 1248, 1164, 915, 824, 784, 730 cm−1; 1H NMR (CDCl3) δ 4.39 (s, CH2N), 4.59-4.74 (br m, NH), 6.57 (d, J=8.8 Hz, 2H3), 6.94-7.05 (m, 2 ArH), 7.11 (d, J=7.5 Hz, H6′), 7.28-7.36 (m, 1 ArH), 7.42 (d, J=8.8 Hz, 2H2); 13C NMR (CDCl3) δ 46.8 (d, J=1.7 Hz, NCH2), 99.9 (CN), 112.4 (ArC), 113.9 (d, J=22.2 Hz, C4′ or C2′), 114.4 (d, J=21.1 Hz, C2′ or C4′), 120.3 (ArC), 122.5 (d, J=2.9 Hz, C6′), 130.3 (d, J=8.6 Hz, C5′), 133.7 (ArC), 140.6 (d, J=6.8 Hz, C1′), 150.9 (ArC), 163.1 (d, J=245.3 Hz, C3′); HRMS (M+H+) (ESI+) 227.0985 [M+H+] (calcd for C14H11FN2H+227.0984).

後処理

  1. customthe volatiles were evaporated
  2. additionCH2Cl2 (100 mL) and H2O (100 mL) were added
  3. customthe layers separated
  4. washThe aqueous layer was washed with CH2Cl2 (2×100 mL)
  5. customdried
  6. concentrationconcentrated under vacuum
  7. customThe crude residue was purified by column chromatography (SiO2; EtOAc/hexanes 0/10 to 3/7)

出典と根拠

ORDレコード
ord-436f782b345b477fa97546556aef9d35
出典データセット
uspto-grants-2014_09
特許番号
US08829033B2

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