Nitrogen → 1-(3,5-Dichloro-4'-fluoro-biphenyl-4-ylmethyl)-3-piperidin-1-yl-pyrrolidin-2-one

HRID 1670842노트

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HRID 1670842 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.[F:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1.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>[Cl:22][C:4]1[CH:3]=[C:2]([C:27]2[CH:28]=[CH:29][C:24]([F:23])=[CH:25][CH:26]=2)[CH:20]=[C:19]([Cl:21])[C:5]=1[CH2:6][N:7]1[CH2:11][CH2:10][CH:9]([N:12]2[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]2)[C:8]1=[O:18]

참가 물질

8

반응물 3

HCID 947NitrogenHCID 2856454-Fluorophenylboronic acidHCID 576580161-(4-Bromo-2,6-dichloro-benzyl)-3-piperidin-1-yl-pyrrolidin-2-one

생성물 1

HCID 576579971-(3,5-Dichloro-4'-fluoro-biphenyl-4-ylmethyl)-3-piperidin-1-yl-pyrrolidin-2-one수율 32.1%

시약·촉매·용매 4

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

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온도
90 °C

실험 절차

Purge a mixture of 1-(4-bromo-2,6-dichloro-benzyl)-3-piperidin-1-yl-pyrrolidin-2-one (0.150 g, 0.37 mmol) and 4-fluorophenylboronic acid (0.150 g, 1.07 mmol) in toluene (7 mL) and 2M sodium carbonate (1.3 mL) with N2. Treat the reaction with Pd(PPh3)4 (0.043 g, 0.037 mmol) and heat to 90° C. for 4 hours under N2. Cool the reaction, dilute with ethyl acetate, and wash with and water. Dry the organic layer (Na2SO4), remove the solvent in vacuo to afford crude product, and purify with a 0 to 10% methanol in CH2Cl2 gradient to afford 0.050 g (32%) of the titled product. Rf=0.46 (9/1 CH2Cl2/methanol). ES MS (m/z): 421 (M+).

후처리

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

출처 및 근거

ORD 기록
ord-b9e46ba1905d42c88ba5925495ea42c4
출처 데이터셋
uspto-grants-2011_08
특허 번호
US07994176B2

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