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Dichloromethane → 2-amino-5-(4-{[tert-butyl(dimethyl)silyl]oxy}cyclohex-1-en-1-yl)-N,N-dimethylbenzamide

HRID 1947972
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HRID 1947972 반응식
[NH2:1][C:2]1[CH:12]=[CH:11][C:10](B2OC(C)(C)C(C)(C)O2)=[CH:9][C:3]=1[C:4]([N:6]([CH3:8])[CH3:7])=[O:5].[C:22]([Si:26]([CH3:43])([CH3:42])[O:27][CH:28]1[CH2:33][CH2:32][C:31](OS(C(F)(F)F)(=O)=O)=[CH:30][CH2:29]1)([CH3:25])([CH3:24])[CH3:23].ClCCl.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.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]>[NH2:1][C:2]1[CH:12]=[CH:11][C:10]([C:31]2[CH2:32][CH2:33][CH:28]([O:27][Si:26]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:42])[CH3:43])[CH2:29][CH:30]=2)=[CH:9][C:3]=1[C:4]([N:6]([CH3:7])[CH3:8])=[O:5]
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참가 물질

8

반응물 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 534150124-((tert-Butyldimethylsilyl)oxy)cyclohex-1-en-1-yl trifluoromethanesulfonateHCID 574162382-amino-N,N-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide2회

생성물 1

HCID 672614622-amino-5-(4-{[tert-butyl(dimethyl)silyl]oxy}cyclohex-1-en-1-yl)-N,N-dimethylbenzamide

시약·촉매·용매 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 312751,4-Dioxane용매

실험 절차

A solution of 2-amino-N,N-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (Compound 173D: 0.500 g, 1.72 mmol) and trifluoro-methanesulfonic acid 4-(tert-butyl-dimethyl-silanyloxy)-cyclohex-1-enyl ester (WO 2005092863, 0.745 g, 2.07 mmol) in 1,4-dioxane (4 mL) and H2O (1 mL) was charged with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (0.063 g, 0.086 mmol) and potassium carbonate (0.71 g, 5.2 mmol) in a microwave vial. The reaction mixture was evacuated and purged with nitrogen (3×) and irradiated in the microwave for 30 min at 100° C. The reaction mixture was partitioned between EtOAc and water and separated. The aqueous was extracted with EtOAc (3×) and the combined organic fractions were washed with brine, dried over sodium sulfate, filtered, and concentrated. The compound was purified on an Isco Combiflash eluting with 50 to 100% EtOAc in heptane to afford the title compound. 1H NMR (400 MHz, DMSO-d6) δ 7.17 (dd, J=2.27, 8.59 Hz, 1H), 7.00 (d, J=2.27 Hz, 1H), 6.64 (d, J=8.59 Hz, 1H), 5.83 (d, J=2.02 Hz, 1H), 5.16 (s, 2H), 3.89-3.98 (m, 1H), 2.91 (br. s., 6H), 2.32-2.44 (m, 2H), 2.00-2.09 (m, 1H), 1.85 (d, J=10.86 Hz, 1H), 1.55-1.67 (m, 1H), 0.87 (s, 12H), 0.06 (d, J=2.27 Hz, 6H); MS (ES±): m/z: 375.2372 [MH+]. HPLC: tR=1.96 min (UPLC TOF MS: polar—3 min).

후처리

  1. customThe reaction mixture was evacuated
  2. custompurged with nitrogen (3×)
  3. customirradiated in the microwave for 30 min at 100° C
  4. customThe reaction mixture was partitioned between EtOAc and water
  5. customseparated
  6. extractionThe aqueous was extracted with EtOAc (3×)
  7. washthe combined organic fractions were washed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe compound was purified on an Isco Combiflash
  12. washeluting with 50 to 100% EtOAc in heptane

출처 및 근거

ORD 기록
ord-d2499743154644aca4fdad13e5ce4617
출처 데이터셋
uspto-grants-2013_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08399433B2

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