Binap, (A+-)- → 4-(1'-Cyclopropylmethyl-2'-oxo-3,4,5,6,1',2'-hexahydro-2H-[1,4']bipyridinyl-4-yl)-benzoic acid

HRID 516632노트

반응식

HRID 516632 반응식
C[O:2][C:3](=[O:16])[C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[CH:6][CH:5]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.Br[C:64]1[CH:69]=[CH:68][N:67]([CH2:70][CH:71]2[CH2:73][CH2:72]2)[C:66](=[O:74])[CH:65]=1>C1(C)C=CC=CC=1.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:71]1([CH2:70][N:67]2[CH:68]=[CH:69][C:64]([N:13]3[CH2:14][CH2:15][CH:10]([C:7]4[CH:8]=[CH:9][C:4]([C:3]([OH:2])=[O:16])=[CH:5][CH:6]=4)[CH2:11][CH2:12]3)=[CH:65][C:66]2=[O:74])[CH2:72][CH2:73]1

참가 물질

7

반응물 3

HCID 634876Binap, (A+-)-HCID 24904226Methyl 4-(piperidin-4-yl)benzoateHCID 585545154-Bromo-1-(cyclopropylmethyl)pyridin-2(1H)-one

생성물 1

HCID 594971014-(1'-Cyclopropylmethyl-2'-oxo-3,4,5,6,1',2'-hexahydro-2H-[1,4']bipyridinyl-4-yl)-benzoic acid

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

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온도
100 °C

실험 절차

4-Piperidin-4-ylbenzoic acid methyl ester (0.40 g, 1.81 mmol), palladium(II) acetate (0.015 g, 0.069 mmol) sodium tert-butoxide (0.34 g, 3.44 mmol) and BINAP (0.06 g, 0.096 mmol) were added to a stirred solution of intermediate D3 (0.31 g, 1.37 mmol) in toluene (10 ml). The reaction mixture was heated at 100° C. for 16 hours in a sealed tube. After cooling to room temperature the mixture was diluted with EtOAc and then filtered through diatomaceous earth, after which the solvent was evaporated in vacuo. The crude residue was treated with a mixture of DCM/methanol and then filtered off. The filtrate was evaporated to dryness in vacuo to yield crude D37 (0.48 g, 100%) that was used without further purification.

후처리

  1. temperatureAfter cooling to room temperature the mixture
  2. filtrationfiltered through diatomaceous earth
  3. customafter which the solvent was evaporated in vacuo
  4. additionThe crude residue was treated with a mixture of DCM/methanol
  5. filtrationfiltered off
  6. customThe filtrate was evaporated to dryness in vacuo
  7. customto yield crude D37 (0.48 g, 100%) that
  8. customwas used without further purification

출처 및 근거

ORD 기록
ord-d16722e9cdfe4f48b81966a258081f79
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09114138B2

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