Benzoyl Peroxide → 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-5-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carbonitrile

HRID 333221ノート

反応式

HRID 333221 の反応式
[C:1]([C:3]1[C:12]([F:13])=[CH:11][CH:10]=[C:9]([CH3:14])[C:4]=1[C:5]([O:7]C)=O)#[N:2].BrN1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.C(N(CC)CC)C.[F:48][C:49]1([F:62])[CH2:54][CH2:53][CH:52]([N:55]2[CH2:60][CH2:59][CH:58]([NH2:61])[CH2:57][CH2:56]2)[CH2:51][CH2:50]1>C(OC)(=O)C(C)(C)C.ClCCl.ClCCl.C(O)C>[F:62][C:49]1([F:48])[CH2:54][CH2:53][CH:52]([N:55]2[CH2:56][CH2:57][CH:58]([N:61]3[C:5](=[O:7])[C:4]4[C:3]([C:1]#[N:2])=[C:12]([F:13])[CH:11]=[CH:10][C:9]=4[CH2:14]3)[CH2:59][CH2:60]2)[CH2:51][CH2:50]1

参加物

9

反応物 5

HCID 7187Benzoyl PeroxideHCID 8471TriethylamineHCID 67184N-bromobutanimideHCID 67192265Methyl 2-cyano-3-fluoro-6-methylbenzoateHCID 671942361-(4,4-Difluorocyclohexyl)-piperidin-4-ylamine

生成物 1

HCID 696741452-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-5-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carbonitrile収率 60.6%

試薬・触媒・溶媒 3

HCID 6344Dichloromethane溶媒HCID 69027Methyl pivalate溶媒HCID 21584144Dichloromethane ethanol溶媒

反応条件

温度
85 °C

実験手順

To a solution of methyl 2-cyano-3-fluoro-6-methylbenzoate (208 mg, 1.07 mmol) in methyl pivalate (2 mL), N-bromosuccinimide (310 mg, 1.74 mmol) and benzoylperoxide (20 mg, 0.097 mmol) were added. The reaction mixture was stirred at 85° C. under nitrogen atmosphere for 3 hours. Crude was filtered on Gooch and washed with toluene. Volatiles were evaporated and the residue was dissolved in acetonitrile (3 mL). Triethylamine (0.41 mL, 2.9 mmol) and 1-(4,4-difluorocyclohexyl)-piperidin-4-ylamine (280 mg, 0.97 mmol) were added and the reaction mixture was stirred at 90° C. for 3 hours. Crude was diluted with dichloromethane and washed with 15% ammonium hydroxide Organic phase was dried over sodium sulfate, filtered and evaporated. Column chromatography (dichloromethane/ethanol:95/5) afforded title compound (222 mg, 60% yield).

後処理

  1. filtrationCrude was filtered on Gooch
  2. washwashed with toluene
  3. customVolatiles were evaporated
  4. dissolutionthe residue was dissolved in acetonitrile (3 mL)
  5. stirringthe reaction mixture was stirred at 90° C. for 3 hours
  6. washwashed with 15% ammonium hydroxide Organic phase
  7. dry with materialwas dried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated

出典と根拠

ORDレコード
ord-fe41265c19794c67b35eb10316e5112e
出典データセット
uspto-grants-2014_11
特許番号
US08877944B2

反応ノート

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