Dichloromethane → 5-{5-[(4-benzyl-4-hydroxypiperidin-1-yl)methyl]2-thienyl}2-tertbutylisothiazol-3(2H)-one 1,1-dioxide trifluoroacetate

HRID 724621노트

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HRID 724621 반응식
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH2:8]([C:15]1([OH:30])[CH2:20][CH2:19][N:18]([CH2:21][C:22]2[S:26][C:25](B(O)O)=[CH:24][CH:23]=2)[CH2:17][CH2:16]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[C:31]([N:35]1[C:39](=[O:40])[CH:38]=[C:37](Cl)[S:36]1(=[O:43])=[O:42])([CH3:34])([CH3:33])[CH3:32].C(=O)([O-])[O-].[K+].[K+].ClCCl>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH2:8]([C:15]1([OH:30])[CH2:20][CH2:19][N:18]([CH2:21][C:22]2[S:26][C:25]([C:37]3[S:36](=[O:42])(=[O:43])[N:35]([C:31]([CH3:33])([CH3:32])[CH3:34])[C:39](=[O:40])[CH:38]=3)=[CH:24][CH:23]=2)[CH2:17][CH2:16]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

참가 물질

7

반응물 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 218786382-Tert-butyl-5-chloro-2,3-dihydro-1lambda6,2-thiazole-1,1,3-trioneHCID 69597789{5-[(4-Benzyl-4-hydroxypiperidin-1-yl)methyl]-2-thienyl}boronic acid trifluoroacetate

생성물 1

HCID 695978815-{5-[(4-benzyl-4-hydroxypiperidin-1-yl)methyl]2-thienyl}2-tertbutylisothiazol-3(2H)-one 1,1-dioxide trifluoroacetate수율 17%

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 312751,4-Dioxane용매

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온도
80 °C

실험 절차

A solution of 4.12-A (100 mg, 0.2 mmol), 9-A (55 mg, 0.25 mmol), potassium carbonate (190 mg, 1.3 mmol) in 1,4-dioxane (1.5 mL) was added to a vial and degassed with nitrogen. Then [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (28 mg, 0.034 mmol) was added, degassed with nitrogen and the vial capped and heated at 80° C. overnight. The reaction mixture was filtered through silica gel and eluted with copious amounts of EtOAc. The solvent was concentrated and crude sample purified by reverse phase HPLC to afford 20 mg (15%) of 4.12-B. LCMS found for C24H30N2O4S2 (M+H)+: m/z=475.

후처리

  1. customdegassed with nitrogen
  2. customdegassed with nitrogen
  3. customthe vial capped
  4. filtrationThe reaction mixture was filtered through silica gel
  5. washeluted with copious amounts of EtOAc
  6. concentrationThe solvent was concentrated
  7. customcrude sample purified by reverse phase HPLC

출처 및 근거

ORD 기록
ord-5da0916eddb9466d8523fdbf9746e7dc
출처 데이터셋
uspto-grants-2006_11
특허 번호
US07141596B2

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