Sodium Carbonate → 5-(3,4-Dichloro-phenyl)-N-((1S,2R)-2-hydroxy-cyclohexyl)-6-(2,2,2-trifluoro-ethoxy)-nicotinamide

HRID 1516383ノート

反応式

HRID 1516383 の反応式
Br[C:2]1[C:3]([O:18][CH2:19][C:20]([F:23])([F:22])[F:21])=[N:4][CH:5]=[C:6]([CH:17]=1)[C:7]([NH:9][C@H:10]1[CH2:15][CH2:14][CH2:13][CH2:12][C@H:11]1[OH:16])=[O:8].[Cl:24][C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][C:30]=1[Cl:31].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.CN(C=O)C.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C(Cl)Cl>[Cl:24][C:25]1[CH:26]=[C:27]([C:2]2[C:3]([O:18][CH2:19][C:20]([F:23])([F:22])[F:21])=[N:4][CH:5]=[C:6]([CH:17]=2)[C:7]([NH:9][C@H:10]2[CH2:15][CH2:14][CH2:13][CH2:12][C@H:11]2[OH:16])=[O:8])[CH:28]=[CH:29][C:30]=1[Cl:31]

参加物

7

反応物 3

HCID 10340Sodium CarbonateHCID 27343303,4-Dichlorobenzeneboronic acidHCID 698122955-Bromo-N-((1S,2R)-2-hydroxy-cyclohexyl)-6-(2,2,2-trifluoro-ethoxy)-nicotinamide

生成物 1

HCID 509390545-(3,4-Dichloro-phenyl)-N-((1S,2R)-2-hydroxy-cyclohexyl)-6-(2,2,2-trifluoro-ethoxy)-nicotinamide収率 67.8%

試薬・触媒・溶媒 3

HCID 178418807HCID 178418807、化合物触媒HCID 1140Toluene溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
90 °C

実験手順

5-Bromo-N-((1S,2R)-2-hydroxy-cyclohexyl)-6-(2,2,2-trifluoro-ethoxy)-nicotinamide (42.0 g, 106 mmol) was dissolved in toluene (1900 mL) and DMF (100 mL). To this solution was added with stirring [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) CH2Cl2 (0.9 g, 1.06 mmol), 3,4-dichlorophenylboronic acid (20.2 g, 106 mmol) and sodium carbonate solution (2M, 106 mL). This mixture was heated to 90° C. for 2 h, cooled to room temperature and partitioned between ethyl acetate (1000 mL) and water (2000 mL), the water phase was separated, extracted twice more with ethyl acetate (2×1000 mL) and the organic phases were washed once with water and once with brine (1000 mL each). Organic phases were pooled, dried with MgSO4 and the volatiles removed in vacuo. The residue was dissolved in diethyl ether (500 mL) and filtered through diatomaceous earth. The title compound precipitated when n-heptane (500 mL) was added drop wise to the diethyl ether solution, was filtered off and dried in vacuo to give 33.3 g the title compound as an off-white solid; MS 463.079 (M+H)+.

後処理

  1. temperaturecooled to room temperature
  2. custompartitioned between ethyl acetate (1000 mL) and water (2000 mL)
  3. customthe water phase was separated
  4. extractionextracted twice more with ethyl acetate (2×1000 mL)
  5. washthe organic phases were washed once with water and once with brine (1000 mL each)
  6. dry with materialdried with MgSO4
  7. customthe volatiles removed in vacuo
  8. dissolutionThe residue was dissolved in diethyl ether (500 mL)
  9. filtrationfiltered through diatomaceous earth
  10. customThe title compound precipitated when n-heptane (500 mL)
  11. additionwas added drop wise to the diethyl ether solution
  12. filtrationwas filtered off
  13. customdried in vacuo

出典と根拠

ORDレコード
ord-b0b4e41d5bd7418f8102e29af9df4bf5
出典データセット
uspto-grants-2012_07
特許番号
US08227491B2

反応ノート

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