Cesium carbonate → 1-Methyl-4-[2-methyl-4-nitro-5-(propan-2-yloxy)phenyl]piperazine

HRID 518824노트

반응식

HRID 518824 반응식
C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.[CH3:49][N:50]1[CH2:55][CH2:54][NH:53][CH2:52][CH2:51]1.Cl[C:57]1[CH:62]=[C:61]([O:63][CH:64]([CH3:66])[CH3:65])[C:60]([N+:67]([O-:69])=[O:68])=[CH:59][C:58]=1[CH3:70]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:49][N:50]1[CH2:55][CH2:54][N:53]([C:57]2[CH:62]=[C:61]([O:63][CH:64]([CH3:65])[CH3:66])[C:60]([N+:67]([O-:69])=[O:68])=[CH:59][C:58]=2[CH3:70])[CH2:52][CH2:51]1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 531671-MethylpiperazineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 457903241-Chloro-5-isopropoxy-2-methyl-4-nitrobenzene2회

생성물 1

HCID 866979901-Methyl-4-[2-methyl-4-nitro-5-(propan-2-yloxy)phenyl]piperazine수율 57.5%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매

실험 절차

24.9 g of caesium carbonate, 745 mg of palladium acetate, 2.88 g of (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphane) and 4.89 g of 1-methylpiperazine are added to a solution of 7.62 g of 1-chloro-2-methyl-4-nitro-5-(propan-2-yloxy)benzene (prepared according to WO2008/073687, p. 31) in 380 ml of dioxane under argon. The mixture is refluxed for 5.5 h, and then cooled to ambient temperature. The mixture is combined with the crude product of one and the same reaction carried out on 1.89 g of 1-chloro-2-methyl-4-nitro-5-(propan-2-yloxy)benzene under the same conditions. The mixture is concentrated under vacuum and the residue is taken up with 100 ml of water, 200 ml of ethyl acetate and a little methanol. The mixture is filtered on Clarcel and the aqueous phase is extracted twice with 100 ml of ethyl acetate. The combined organic phases are washed with 100 ml of a saturated sodium chloride solution, dried over magnesium sulfate and concentrated under vacuum. The crude product is purified on 340 g of silica, elution being carried out with 0-100% of acetone in dichloromethane, so as to obtain 5.60 g of 1-methyl-4-[2-methyl-4-nitro-5-(propan-2-yloxy)phenyl]piperazine in the form of a black solid.

후처리

  1. temperatureThe mixture is refluxed for 5.5 h
  2. customthe same reaction
  3. concentrationThe mixture is concentrated under vacuum
  4. filtrationThe mixture is filtered on Clarcel
  5. extractionthe aqueous phase is extracted twice with 100 ml of ethyl acetate
  6. washThe combined organic phases are washed with 100 ml of a saturated sodium chloride solution
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated under vacuum
  9. customThe crude product is purified on 340 g of silica, elution

출처 및 근거

ORD 기록
ord-41859a61d4f8408fa520ebbc055592cc
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09115140B2

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