Nitrogen → 3',5'-Dichloro-4'-(2-oxo-3-piperidin-1-yl-pyrrolidin-1-ylmethyl)-biphenyl-4-carboxylic acid methyl ester

HRID 1670843노트

반응식

HRID 1670843 반응식
Br[C:2]1[CH:20]=[C:19]([Cl:21])[C:5]([CH2:6][N:7]2[CH2:11][CH2:10][CH:9]([N:12]3[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]3)[C:8]2=[O:18])=[C:4]([Cl:22])[CH:3]=1.[CH3:23][O:24][C:25]([C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1)=[O:26].N#N>C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:23][O:24][C:25]([C:27]1[CH:32]=[CH:31][C:30]([C:2]2[CH:20]=[C:19]([Cl:21])[C:5]([CH2:6][N:7]3[CH2:11][CH2:10][CH:9]([N:12]4[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]4)[C:8]3=[O:18])=[C:4]([Cl:22])[CH:3]=2)=[CH:29][CH:28]=1)=[O:26]

참가 물질

8

반응물 3

HCID 947NitrogenHCID 27343694-Methoxycarbonylphenylboronic acidHCID 576580161-(4-Bromo-2,6-dichloro-benzyl)-3-piperidin-1-yl-pyrrolidin-2-one

생성물 1

HCID 576580003',5'-Dichloro-4'-(2-oxo-3-piperidin-1-yl-pyrrolidin-1-ylmethyl)-biphenyl-4-carboxylic acid methyl ester수율 39%

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매HCID 10340Sodium Carbonate용매

반응 조건

온도
90 °C

실험 절차

Purge a mixture of 1-(4-bromo-2,6-dichloro-benzyl)-3-piperidin-1-yl-pyrrolidin-2-one (0.429 g, 1.06 mmol) and 4-methoxycarbonyl phenylboronic acid (0.57 g, 3.16 mmol) in toluene (15 mL) and 2M sodium carbonate (3.7 mL) with N2. Treat the reaction with Pd(PPh3)4 (0.061 g, 0.053 mmol) and heat to 90° C. for 7 hours under N2. Cool the reaction, dilute with ethyl acetate, and wash with water. Dry the organic layer (Na2SO4), remove the solvent in vacuo afford crude product, and purify with a 0 to 10% methanol in CH2Cl2 gradient to afford 0.19 g (39%) of the titled product. Rf=0.40 (9/1 CH2Cl2/methanol). ES MS (m/z): 461 (M+).

후처리

  1. customPurge
  2. additionTreat
  3. temperatureCool
  4. customthe reaction
  5. washwash with water
  6. dry with materialDry the organic layer (Na2SO4)
  7. customremove the solvent in vacuo
  8. customafford crude product
  9. custompurify with a 0 to 10% methanol in CH2Cl2 gradient

출처 및 근거

ORD 기록
ord-9c6de28b02c245a9ad8e45e0f7fd1b18
출처 데이터셋
uspto-grants-2011_08
특허 번호
US07994176B2

반응 노트

불러오는 중…