Sodium Carbonate → 1-((4R,5R)-5-{4-[6-(1-Benzylamino-2,2,2-trifluoro-ethyl)-pyridin-3-yl]-phenyl}-4-fluoromethyl-2,2-dimethyl-oxazolidin-3-yl)-2,2-difluoro-ethanone

HRID 525563Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 525563
[CH2:1]([NH:8][CH:9]([C:14]1[CH:19]=[CH:18][C:17](Br)=[CH:16][N:15]=1)[C:10]([F:13])([F:12])[F:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:21][CH:22]([F:49])[C:23]([N:25]1[C@H:29]([CH2:30][F:31])[C@@H:28]([C:32]2[CH:37]=[CH:36][C:35](B3OC(C)(C)C(C)(C)O3)=[CH:34][CH:33]=2)[O:27][C:26]1([CH3:48])[CH3:47])=[O:24].C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.O.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>[CH2:1]([NH:8][CH:9]([C:14]1[N:15]=[CH:16][C:17]([C:35]2[CH:36]=[CH:37][C:32]([C@H:28]3[O:27][C:26]([CH3:48])([CH3:47])[N:25]([C:23](=[O:24])[CH:22]([F:49])[F:21])[C@H:29]3[CH2:30][F:31])=[CH:33][CH:34]=2)=[CH:18][CH:19]=1)[C:10]([F:13])([F:12])[F:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 866954142,2-difluoro-1-((4S,5R)-4-(fluoromethyl)-2,2-dimethyl-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)oxazolidin-3-yl)ethanoneHCID 86695446Benzyl-[1-(5-bromo-pyridin-2-yl)-2,2,2-trifluoro-ethyl]-amine

Produkt 1

HCID 866954451-((4R,5R)-5-{4-[6-(1-Benzylamino-2,2,2-trifluoro-ethyl)-pyridin-3-yl]-phenyl}-4-fluoromethyl-2,2-dimethyl-oxazolidin-3-yl)-2,2-difluoro-ethanoneAusbeute 92,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 86587398Ethanol toluene waterLösungsmittel

Versuchsvorschrift

To a stirred solution of Benzyl-[1-(5-bromo-pyridin-2-yl)-2,2,2-trifluoro-ethyl]-amine (0.15 g, 0.43 mmol) and 2,2-Difluoro-1-{(4S,5R)-4-fluoromethyl-2,2-dimethyl-5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-oxazolidin-3-yl}-ethanone (0.18 g, 0.43 mmol) in toluene:ethanol:water (1:1:1; 7:7:7 mL) is added Na2CO3 (0.11 g, 1.08 mmol) at room temperature. Resulting reaction mixture is degassed with nitrogen for 30 minutes then added Pd(PPh3)4 (0.05 g, 0.043 mmol) and mixture is heated to 80° C. for 3 hours. Reaction mixture is concentrated in vacuo and crude material is purified by combi-flash eluting in 20% Ethyl acetate in Hexane to afford the title compound (0.22 g). 1H NMR (400 MHz, DMSO) δ: 1.52 (s, 3H), 1.60 (s, 3H), 3.59-3.69 (m, 2H), 3.73-3.78 (m, 1H), 4.47-4.51 (m, 0.5H), 4.55-4.59 (m, 0.5H), 4.66-4.72 (m, 1H), 4.75-4.79 (m, 0.5H), 4.80-4.93 (m, 0.5H), 5.28 (d, J=3.68 Hz 1H), 6.65 (t, J=51.92 Hz, 1H) 7.23-7.24 (m, 2H), 7.26-7.31 (m, 3H), 7.56-7.62 (m, 3H), 7.75 (d, J=8.16 Hz, 1H), 8.06 (s, 1H), 8.16 (d, J=8.32 Hz 1H), 8.73 (s, 1H). LC-MS (m/z): [M+H]=552.1.

Aufarbeitung

  1. customResulting
  2. customreaction mixture
  3. customis degassed with nitrogen for 30 minutes
  4. customReaction mixture
  5. concentrationis concentrated in vacuo and crude material
  6. customis purified by combi-flash
  7. washeluting in 20% Ethyl acetate in Hexane

Quellen und Nachweise

ORD-Eintrag
ord-c6c0102e662a442f8a781ea6f2b75a04
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09340564B2

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