Binap, (A+-)- → 2,4,6-trifluoro-N-methyl-N-[6-(1-t-butoxycarbonyl-piperidin-4-ylcarbonyl)-pyridin-2-yl]-benzamide

HRID 404236

反応式

HRID 404236 の反応式
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)=[O:9])[N:3]=1.[CH3:23][NH:24][C:25](=[O:35])[C:26]1[C:31]([F:32])=[CH:30][C:29]([F:33])=[CH:28][C:27]=1[F:34].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.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:32][C:31]1[CH:30]=[C:29]([F:33])[CH:28]=[C:27]([F:34])[C:26]=1[C:25]([N:24]([CH3:23])[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)=[O:9])[N:3]=1)=[O:35]

参加物

7

反応物 4

HCID 634876Binap, (A+-)-2 回HCID 179803442,4,6-trifluoro-N-methylbenzamide2 回HCID 23676156Sodium t-butoxide2 回HCID 866009232-Bromo-6-(1-t-butoxycarbonylpiperidin-4-ylcarbonyl)-pyridine

生成物 1

HCID 674431142,4,6-trifluoro-N-methyl-N-[6-(1-t-butoxycarbonyl-piperidin-4-ylcarbonyl)-pyridin-2-yl]-benzamide収率 44%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒2 回HCID 1140Toluene溶媒

実験手順

Heat a mixture of 2-bromo-6-(1-t-butoxycarbonylpiperidin-4-ylcarbonyl)-pyridine (152 mg, 0.41 mmol), N-methyl-2,4,6-trifluorobenzamide (92.6 mg, 0.49 mmol), Pd2(dba)3 (9.2 mg, 0.01 mmol), BINAP (12.4 mg, 0.02 mmol), sodium t-butoxide (55 mg, 0.57 mmol) in anhydrous toluene (10 mL) at 85° C. for 16 hrs. Cool the reaction to room temperature and add another aliquot of N-methyl-2,4,6-trifluorobenzamide, Pd2(dba)3, BINAP and sodium t-butoxide in the same amount. Re-heat the reaction at 85° C. for 16 more hours. Extract the reaction mixture with ethyl acetate and aqueous NaOH (0.1N). Collect and dry the organic layers. Concentrate and purify the crude product by chromatography (silica gel, 10%-30% ethyl acetate/hexane) to obtain 2,4,6-trifluoro-N-methyl-N-[6-(1-t-butoxycarbonyl-piperidin-4-ylcarbonyl)-pyridin-2-yl]-benzamide (86 mg, 44% yield).

後処理

  1. temperatureHeat
  2. temperatureCool
  3. customthe reaction to room temperature
  4. customRe-heat the reaction at 85° C. for 16 more hours
  5. extractionExtract the reaction mixture with ethyl acetate and aqueous NaOH (0.1N)
  6. customCollect
  7. customdry the organic layers
  8. concentrationConcentrate
  9. custompurify the crude product by chromatography (silica gel, 10%-30% ethyl acetate/hexane)

出典と根拠

ORDレコード
ord-bd087da251f14d4ea24fa897cfdee75b
出典データセット
uspto-grants-2014_06
特許番号
US08748459B2

関連ノート

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