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

HRID 1667342

반응식

HRID 1667342 반응식
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]

참가 물질

7

반응물 4

HCID 634876Binap, (A+-)-2회HCID 179803442,4,6-trifluoro-N-methylbenzamide2회HCID 23676156Sodium t-butoxide2회HCID 866009232-Bromo-6-(1-t-butoxycarbonylpiperidin-4-ylcarbonyl)-pyridine

생성물 1

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

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매2회HCID 1140Toluene용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-e8afdd8ae4ea437483661fe14ab15115
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08044207B2

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