Cesium carbonate → 1-(3-(1,3-Dioxolan-2-yl)-5-(trifluoromethoxy)phenyl)-4-isopropylpiperazine

HRID 922383ノート

反応式

HRID 922383 の反応式
Br[C:2]1[CH:3]=[C:4]([CH:13]2[O:17][CH2:16][CH2:15][O:14]2)[CH:5]=[C:6]([O:8][C:9]([F:12])([F:11])[F:10])[CH:7]=1.[CH:18]([N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1)([CH3:20])[CH3:19].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[O:14]1[CH2:15][CH2:16][O:17][CH:13]1[C:4]1[CH:3]=[C:2]([N:24]2[CH2:25][CH2:26][N:21]([CH:18]([CH3:20])[CH3:19])[CH2:22][CH2:23]2)[CH:7]=[C:6]([O:8][C:9]([F:12])([F:11])[F:10])[CH:5]=1

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 780131-IsopropylpiperazineHCID 634876Binap, (A+-)-HCID 867193482-[3-Bromo-5-(trifluoromethoxy)phenyl]-1,3-dioxolane

生成物 1

HCID 867193491-(3-(1,3-Dioxolan-2-yl)-5-(trifluoromethoxy)phenyl)-4-isopropylpiperazine収率 70%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

Tris(dibenzylideneacetone)dipalladium(0) (363 mg, 0.396 mmol) was added to a suspension of 2-(3-bromo-5-(trifluoromethoxy)phenyl)-1,3-dioxolane (21, 1.24 g, 3.96 mmol), isopropylpiperazine (610 mg, 4.75 mmol), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (rac-BINAP, 345 mg, 0.554 mmol), cesium carbonate (2.58 g, 7.92 mmol) and anhydrous toluene (50 mL). The mixture was placed under nitrogen and heated to 100° C. for 17 h. The solvent was removed in vacuo and methanol (30 mL) and silica gel (30 g) were added. After removing the methanol the adsorbed crude product was purified by silica gel chromatography eluting with 0-60% EtOAc in hexanes to afford the title compound (996 mg, 70%) as an orange oil: 1H NMR (500 MHz, CDCl3) δ 6.93 (s, 1H), 6.78 (s, 1H), 6.68 (s, 1H), 5.77 (s, 1H), 4.17-3.99 (m, 4H), 3.26-3.22 (m, 4H), 2.72 (sept, 1H), 2.68-2.62 (m, 4H), 1.08 (d, J=6.5 Hz, 6H).

後処理

  1. customThe solvent was removed in vacuo and methanol (30 mL) and silica gel (30 g)
  2. additionwere added
  3. customAfter removing the methanol the adsorbed crude product
  4. customwas purified by silica gel chromatography
  5. washeluting with 0-60% EtOAc in hexanes

出典と根拠

ORDレコード
ord-eecd8dca9bd24397941c1c032c4b3412
出典データセット
uspto-grants-2016_03
特許番号
US09278940B2

反応ノート

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