Cesium carbonate → (4S,5R)-5-[4-(6-Cyano-pyridin-3-yl)-phenyl]-4-fluoromethyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester

HRID 1487514Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1487514
[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][F:14])[C@@H:11]([C:15]2[CH:20]=[CH:19][C:18](B3OC(C)(C)C(C)(C)O3)=[CH:17][CH:16]=2)[O:10][C:9]1([CH3:31])[CH3:30])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].Br[C:39]1[CH:40]=[CH:41][C:42]([C:45]#[N:46])=[N:43][CH:44]=1>C(COC)OC.O.O.C(OCC)(=O)C.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>[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][F:14])[C@@H:11]([C:15]2[CH:16]=[CH:17][C:18]([C:39]3[CH:44]=[N:43][C:42]([C:45]#[N:46])=[CH:41][CH:40]=3)=[CH:19][CH:20]=2)[O:10][C:9]1([CH3:30])[CH3:31])=[O:7])([CH3:3])([CH3:4])[CH3:2]

Komponenten

8

Edukt 3

HCID 10796Cesium carbonateHCID 8171545-Bromopyridine-2-carbonitrileHCID 58631114(4S,5R)-Rel-tert-butyl4-(fluoromethyl)-2,2-dimethyl-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)oxazolidine-3-carboxylate

Produkt 1

HCID 86695461(4S,5R)-5-[4-(6-Cyano-pyridin-3-yl)-phenyl]-4-fluoromethyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl esterAusbeute 42,4 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 18180031Water 1,2-dimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

To stirred solution of (4S,5R)-4-Fluoromethyl-2,2-dimethyl-5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-oxazolidine-3-carboxylic acid tert-butyl ester (0.75 g, 1.72 mmol) in dimethoxyethane:water (8:2, 10 mL) is added Cs2CO3 (1.12 g, 3.44 mmol) and 5-Bromo-pyridine-2-carbonitrile (0.347 g, 1.89 mmol). Reaction mixture is degassed with nitrogen for 30 minutes, followed by addition of Pd(PPh3)4 (0.199 g, 0.172 mmol). The resulting reaction mixture heated to 90° C. for 3 hours. Diluted with water (20 mL) and ethyl acetate (40 mL). The organic layer is separated, dried over sodium sulphate and solvent is evaporated in vacuo to get crude material purified by column chromatography eluting in 15% ethyl acetate in hexane to afford title compound (0.3 g). 1H-NMR (400 MHz, DMSO-d6): δ: 1.43 (s, 9H), 1.51 (s, 3H), 1.63 (s, 3H), 3.83-3.90 (m, 1H), 4.47-4.58 (m, 2H), 4.75-4.93 (m, 2H), 5.15 (d, 1H, J=7.2 Hz), 7.64 (d, 2H, J=8.28 Hz), 7.87 (d, 2H, J=8.24 Hz), 8.15 (d, 1H, J=8.16 Hz), 8.36 (dd, 1H, J=8.2 Hz, J=2.2 Hz), 9.12 (d, 1H, J=2.24 Hz), LC-MS (m/z): [M+H]=412.1.

Aufarbeitung

  1. customReaction mixture
  2. customis degassed with nitrogen for 30 minutes
  3. customThe resulting reaction mixture
  4. customThe organic layer is separated
  5. dry with materialdried over sodium sulphate and solvent
  6. customis evaporated in vacuo
  7. customto get crude material
  8. custompurified by column chromatography
  9. washeluting in 15% ethyl acetate in hexane

Quellen und Nachweise

ORD-Eintrag
ord-6949048d96cf46f298f994553f39cb39
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09428528B2

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