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

HRID 1262415노트

반응식

HRID 1262415 반응식
[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

참가 물질

10

반응물 5

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

생성물 1

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

시약·촉매·용매 4

HCID 23938Palladium촉매HCID 887Methanol용매HCID 8857Ethyl Acetate용매HCID 131727349Sodium bicarbonate brine water용매

반응 조건

온도
79 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-b772bcf33bb841bf9f32f6949be32c87
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08471005B2

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