1,2-Dichloroethane → 2-(4-Amino-phenyl)-2,2-difluoro-1-(4-methyl-piperazin-1-yl)-ethanone

HRID 1262415ノート

反応式

HRID 1262415 の反応式
[F:1][C:2]([F:15])([C:6]1[CH:11]=[CH:10][C:9]([N+:12]([O-])=O)=[CH:8][CH:7]=1)[C:3]([OH:5])=O.S(Cl)(Cl)=O.[CH3:20][N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.C(N(CC)C(C)C)(C)C.ClCCCl>CCOC(C)=O.O.[Cl-].[Na+].O.C([O-])(O)=O.[Na+].[Pd].CO>[NH2:12][C:9]1[CH:10]=[CH:11][C:6]([C:2]([F:1])([F:15])[C:3]([N:24]2[CH2:25][CH2:26][N:21]([CH3:20])[CH2:22][CH2:23]2)=[O:5])=[CH:7][CH:8]=1

参加物

10

反応物 5

HCID 111,2-DichloroethaneHCID 24386Thionyl ChlorideHCID 531671-MethylpiperazineHCID 81531DiisopropylethylamineHCID 467392012,2-Difluoro-2-(4-nitrophenyl)acetic acid

生成物 1

HCID 667124682-(4-Amino-phenyl)-2,2-difluoro-1-(4-methyl-piperazin-1-yl)-ethanone収率 86%

試薬・触媒・溶媒 4

HCID 23938Palladium触媒HCID 887Methanol溶媒HCID 8857Ethyl Acetate溶媒HCID 131727349Sodium bicarbonate brine water溶媒

反応条件

温度
79 °C

実験手順

Difluoro-(4-nitro-phenyl)-acetic acid (106 mg, 0.488 mmol) was suspended in Thionyl chloride (1.00 mL, 13.7 mmol) and heated at 79° C. in a vial for 5 h. Conc. and azeotroping with toluene afforded a residue, which was dried in vacuo. 1-Methyl-piperazine (0.100 mL, 0.902 mmol), N,N-Diisopropylethylamine (0.250 mL, 1.44 mmol) and 1,2-Dichloroethane (1.00 mL, 12.7 mmol) were added to the residue. The mixture was diluted with EtOAc (10 mL) and water:brine:NaHCO3 (1:3:2, 6 mL), the layers separated and the aq. extr. with DCM (2×3 mL). The comb. org. were dried, filtered and conc. in vacuo to give an oil which very slowly crystallizes. The crude amide (124 mg) was shaken under an atmosphere of Hydrogen (15 psi) over 10% Palladium on Carbon (50% Wet) (24 mg, 0.011 mmol) in Methanol (10.0 mL) overnight. Filtration and conc. afforded 2-(4-Amino-phenyl)-2,2-difluoro-1-(4-methyl-piperazin-1-yl)-ethanone (0.113 g; Yield=86.0%) as a film.

後処理

  1. customConc. and azeotroping with toluene
  2. customafforded a residue, which
  3. customwas dried in vacuo
  4. customthe layers separated
  5. customwere dried
  6. filtrationfiltered and conc. in vacuo
  7. customto give an oil which
  8. customvery slowly crystallizes
  9. filtrationFiltration

出典と根拠

ORDレコード
ord-b772bcf33bb841bf9f32f6949be32c87
出典データセット
uspto-grants-2013_06
特許番号
US08471005B2

反応ノート

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