Potassium Carbonate → 3-[(3-Phenoxyphenyl) [[2'-(trifluoromethyl)[1,1'-biphenyl]-3-yl]methyl]amino]-1,1,1-trifluoro-2-propanol

HRID 1018204Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1018204
[O:1]([C:8]1[CH:9]=[C:10]([N:14]([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25](Br)[CH:24]=2)[CH2:15][CH:16]([OH:21])[C:17]([F:20])([F:19])[F:18])[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:30][C:31]([F:42])([F:41])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1B(O)O.C([O-])([O-])=O.[K+].[K+].O(C1C=C(CC(NCC2C=C(C3C=CC=CC=3C(F)(F)F)C=CC=2)(O)C(F)(F)F)C=CC=1)C1C=CC=CC=1>CCO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O.CN(C=O)C.C1(C)C=CC=CC=1>[O:1]([C:8]1[CH:9]=[C:10]([N:14]([CH2:22][C:23]2[CH:24]=[C:25]([C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=3[C:31]([F:42])([F:41])[F:30])[CH:26]=[CH:27][CH:28]=2)[CH2:15][CH:16]([OH:21])[C:17]([F:20])([F:19])[F:18])[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

10

Edukt 4

HCID 11430Potassium CarbonateHCID 27343872-(Trifluoromethyl)benzeneboronic acidHCID 110596773-[(3-Phenoxyphenyl)[[3-bromophenyl]methyl]amino]-1,1,1-trifluoro-2-propanolHCID 88184907(3-Phenoxyphenyl)[[(2'-(trifluoromethyl)[1,1'-biphenyl]-3-yl]methyl]amino]-1,1,1-trifluoro-2-propanol

Produkt 1

HCID 235060473-[(3-Phenoxyphenyl) [[2'-(trifluoromethyl)[1,1'-biphenyl]-3-yl]methyl]amino]-1,1,1-trifluoro-2-propanol

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 702EthanolLösungsmittel2×HCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a toluene (8 mL) solution of 3-[(3-phenoxyphenyl)[[3-bromophenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol (0.51 g, 1.1 mmol) from EX-595B was added 2-(tri-fluoromethyl)phenylboronic acid (0.33 g, 1.7 mmol) and DMF (3 mL). To the resulting solution was added K2CO3 (0.31 g, 2.2 mmol) and Pd(PPh3)4 (0.060 g, 0.05 mmol). The slurry was heated to reflux under argon for 18 h. The cooled mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried (MgSO4) and evaporated to an oil. Purification by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane gave an oil which was dissolved in EtOH, stripped and dried in vacuo to give 0.32 g (55%) of the desired 3-[(3-phenoxyphenyl) [[(2′-(trifluoromethyl)[1,1′-biphenyl]-3-yl]methyl]amino]-1,1,1-tri-fluoro-2-propanol product as a colorless oil. Anal. calcd. for C29H23NO2F6.0.8 EtOH: C, 64.67; H, 4.93; N, 2.46. Found: C, 64.53; H, 4.69; N, 2.49. HRMS calcd. 532.1711 [M+H]+, found: 532.1708. 1H NMR (C6D6) δ1.72 (d, 1H), 3.17 (dd, 1H), 3.46 (dd, 1H), 3.72 (m, 1H), 4.23 (s, 2H), 6.33 (dd, 1H), 6.43 (dd, 1H), 6.52 (t, 1H), 6.82 (m, 2H), 6.9-7.1 (m, 11H), 7.43 (d, 1H).

Aufarbeitung

  1. temperatureThe slurry was heated
  2. temperatureto reflux under argon for 18 h
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried (MgSO4)
  6. customevaporated to an oil
  7. customPurification by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane
  8. customgave an oil which
  9. customdried in vacuo
  10. customto give 0.32 g (55%) of the

Quellen und Nachweise

ORD-Eintrag
ord-944dbb7e34dd46eeafdd29d1e7a0cbf4
Quelldatensatz
uspto-grants-2002_11
Patentnummer
US06479552B2

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