Piperidin-4-ol → 2-[4-(4-Hydroxy-piperidin-1-yl)-2-methyl-phenyl]-8-oxa-2-aza-spiro[4.5]decan-1-one

HRID 1512058노트

반응식

HRID 1512058 반응식
C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.Br[C:36]1[CH:41]=[CH:40][C:39]([N:42]2[CH2:46][CH2:45][C:44]3([CH2:51][CH2:50][O:49][CH2:48][CH2:47]3)[C:43]2=[O:52])=[C:38]([CH3:53])[CH:37]=1.CC(C)([O-])C.[Na+].[NH:60]1[CH2:65][CH2:64][CH:63]([OH:66])[CH2:62][CH2:61]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]>[OH:66][CH:63]1[CH2:64][CH2:65][N:60]([C:36]2[CH:41]=[CH:40][C:39]([N:42]3[CH2:46][CH2:45][C:44]4([CH2:51][CH2:50][O:49][CH2:48][CH2:47]4)[C:43]3=[O:52])=[C:38]([CH3:53])[CH:37]=2)[CH2:61][CH2:62]1

참가 물질

6

반응물 4

HCID 79341Piperidin-4-olHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 584680462-(4-Bromo-2-methyl-phenyl)-8-oxa-2-aza-spiro[4.5]decan-1-one

생성물 1

HCID 584680502-[4-(4-Hydroxy-piperidin-1-yl)-2-methyl-phenyl]-8-oxa-2-aza-spiro[4.5]decan-1-one수율 14.2%

시약·촉매·용매 1

HCID 9811564Bis(dibenzylideneacetone)palladium촉매

실험 절차

An 25-mL round bottom flask containing a stir bar was charged with Pd2(dba)3 (00.01 equiv., 0.0154 mmol, 14 mg.), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl 1 (0.05 equiv., 0.077 mmol, 36.7 mg), 2-(4-bromo-2-methyl-phenyl)-8-oxa-aza-spiro[4.5]decan-1-one (0.50 g, 1.54 mmol, 1 equiv.), and sodium t-butoxide (2.5 equiv., 3.85 mmol, 370 mg.), and piperidin-4-ol (1.5 equiv., 2.3 mmol, 234 mg). The vial was capped with a rubber septum, evacuated and backfilled with N2. To this vial was introduced 8 mL of anhydrous toluene. The reaction was heated in an oil bath set at 90° C. for 2 h, allowed to cool down to room temperature and quenched with water (2 mL). The two layers were separated and the aqueous layer was extracted with DCM (3×10 mL). The combined DCM extracts were washed with sodium bicarbonate (50 mL), and brine (50 mL), dried (anhydrous potassium carbonate), filtered, and concentrated. The crude product was purified by a silica gel column to give 75.1 mg (14% yield) of the title compound as a light yellow solid after standing.

후처리

  1. additionAn 25-mL round bottom flask containing a stir bar
  2. customThe vial was capped with a rubber septum
  3. customevacuated
  4. additionTo this vial was introduced 8 mL of anhydrous toluene
  5. temperatureThe reaction was heated in an oil bath
  6. customquenched with water (2 mL)
  7. customThe two layers were separated
  8. extractionthe aqueous layer was extracted with DCM (3×10 mL)
  9. washThe combined DCM extracts were washed with sodium bicarbonate (50 mL), and brine (50 mL)
  10. dry with materialdried (anhydrous potassium carbonate)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe crude product was purified by a silica gel column

출처 및 근거

ORD 기록
ord-d8d2f26917004b4d906b56f6be33895e
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08217052B2

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