Hydrochloric Acid → N-{4-[2-(2-Hydroxy-ethyl)-phenyl]-pyridin-3-yl}-N-methyl-3,5-bis-trifluoromethyl-benzamide

HRID 878086Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 878086
I[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[N:8]([CH3:25])[C:9](=[O:24])[C:10]1[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]([C:20]([F:23])([F:22])[F:21])[CH:11]=1.[Si]([O:33][CH2:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1B(O)O)(C(C)(C)C)(C)C.C([O-])([O-])=O.[Na+].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl>COCCOC.CCOC(C)=O>[OH:33][CH2:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[N:8]([CH3:25])[C:9](=[O:24])[C:10]1[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]([C:20]([F:23])([F:22])[F:21])[CH:11]=1

Komponenten

8

Edukt 5

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 441193492-(2-(tert-Butyldimethylsilyloxy)ethyl)phenylboronic acidHCID 86670697N-(4-iodopyridin-3-yl)-N-methyl-3,5-bis(trifluoromethyl)benzamide

Produkt 1

HCID 86670723N-{4-[2-(2-Hydroxy-ethyl)-phenyl]-pyridin-3-yl}-N-methyl-3,5-bis-trifluoromethyl-benzamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 80711,2-DimethoxyethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To the solution of N-(4-iodo-pyridin-3-yl)-N-methyl-3,5-bis-trifluoromethyl-benzamide (150 mg, 316 μmol, example 36, intermediate a) in DME (3 mL) was added 2-(2-(tert-butyldimethylsilyloxy)ethyl)phenylboronic acid (88.7 mg, 316 μmol, CAS RN 913835-62-8) and 2M aqueous Na2CO3 solution (1 mL). The reaction mixture was stirred under argon atmosphere for 15 minutes. Pd(II)acetate (3.55 mg, 15.8 μmol) and triphenylphosphine (8.3 mg, 31.6 μmol) were added. The reaction mixture stirred at 90° C. for 18 hours and then poured on 30 mL 1M aqueous HCl and 30 mL EtOAc. The layers were separated and the aqueous layer was extracted a second time with 30 mL EtOAc. The organic layers were washed with 30 mL brine, dried over MgSO4, filtered and concentrated under vacuum. The compound was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:EtOAc (100:0 to 60:40). Colorless solid (95 mg, 52%). MS (ESI): m/z=469.134 [M+H]+.

Aufarbeitung

  1. stirringThe reaction mixture stirred at 90° C. for 18 hours
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted a second time with 30 mL EtOAc
  4. washThe organic layers were washed with 30 mL brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe compound was purified by silica gel chromatography
  9. washeluting with a gradient of n-heptane:EtOAc (100:0 to 60:40)

Quellen und Nachweise

ORD-Eintrag
ord-f908bb983780419098898be772f342a8
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08987307B2

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