Cesium carbonate → 5-(2,4-dichloro-phenyl)-3-hydroxy-1-methyl-1H-pyridin-2-one

HRID 625933

반응식

HRID 625933 반응식
C([O:8][C:9]1[C:10](=[O:17])[N:11]([CH3:16])[CH:12]=[C:13](Br)[CH:14]=1)C1C=CC=CC=1.[Cl:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[C:20]=1B(O)O.C([O-])([O-])=O.[Cs+].[Cs+].[H][H]>C1COCC1.ClCCl.[Pd+2].ClC1C=C[C-](P(C2C=CC=CC=2)C2C=CC=CC=2)C=1Cl.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[Pd]>[Cl:18][C:19]1[CH:20]=[C:21]([Cl:25])[CH:22]=[CH:23][C:24]=1[C:13]1[CH:14]=[C:9]([OH:8])[C:10](=[O:17])[N:11]([CH3:16])[CH:12]=1

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 27343322,6-Dichlorobenzeneboronic acidHCID 674178603-(benzyloxy)-5-bromo-1-methylpyridin-2(1H)-oneHCID 178418361HCID 178418361, 화합물

생성물 1

HCID 533798085-(2,4-dichloro-phenyl)-3-hydroxy-1-methyl-1H-pyridin-2-one수율 11%

시약·촉매·용매 3

HCID 23938Palladium촉매HCID 178478475HCID 178478475, 화합물촉매HCID 8028Tetrahydrofuran용매

실험 절차

To a suspension of 0.045 (0.15 mmol) 3-benzyloxy-5-bromo-1-methyl-1H-pyridin-2-one, 0.44 g (0.23 mmol) 2,6-dichlorophenylboronic acid, and 0.006 g (0.008 mmol) dichloro 1,1′-bis(diphenylphosphino)ferrocene palladium (II) dichloromethane adduct in 2 mL THF was added 1 mL 1 M aq Cs2CO3. The resulting mixture was microwaved to 160° C. for 10 min. After cooling, the organic phase was separated and concentrated and the resulting residue was re-dissolved in MeOH. 0.02 mg (0.019 mmol) 10% Pd/C was added and the resulting suspension was stirred under 1 atm hydrogen gas overnight. The reaction mixture was filtered and concentrated. Purification by automated mass-guided HPLC afforded 0.045 g (11%) 5-(2,4-dichloro-phenyl)-3-hydroxy-1-methyl-1H-pyridin-2-one. 1H NMR (499 MHz, DMSO-d6): δ 9.29 (s, 1 H); 7.71 (d, J=2.13 Hz, 1 H); 7.48 (dd, J=8.32, 2.19 Hz, 1 H); 7.43 (d, J=8.30 Hz, 1 H); 7.34 (d, J=2.35 Hz, 1 H); 6.82 (d, J=2.35 Hz, 1 H); 3.53 (s, 3 H). High resolution mass spec (FT/ICR) calc (M+H)+=270.0084 found 270.0083.

후처리

  1. customThe resulting mixture was microwaved to 160° C. for 10 min
  2. temperatureAfter cooling
  3. customthe organic phase was separated
  4. concentrationconcentrated
  5. dissolutionthe resulting residue was re-dissolved in MeOH
  6. filtrationThe reaction mixture was filtered
  7. concentrationconcentrated
  8. customPurification by automated mass-guided HPLC

출처 및 근거

ORD 기록
ord-a5b4dfc0a29c483dbef69797d64a0485
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09309199B2

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