Sodium Carbonate → 5-(2,4,4-Trimethyl-1,4-dihydro-2H-3,1-benzoxazin-6-yl)thiophene-2-carbonitrile

HRID 2300095Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2300095
Br[C:2]1[CH:3]=[CH:4][C:5]2[NH:10][CH:9]([CH3:11])[O:8][C:7]([CH3:13])([CH3:12])[C:6]=2[CH:14]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Br[C:39]1[S:43][C:42]([C:44]#[N:45])=[CH:41][CH:40]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.[Cl-].[Na+].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].C(OCC)(=O)C>[CH3:11][CH:9]1[O:8][C:7]([CH3:13])([CH3:12])[C:6]2[CH:14]=[C:2]([C:39]3[S:43][C:42]([C:44]#[N:45])=[CH:41][CH:40]=3)[CH:3]=[CH:4][C:5]=2[NH:10]1

Komponenten

10

Edukt 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 35950595-Bromothiophene-2-carbonitrileHCID 234355746-Bromo-2,4,4-trimethyl-2,4-dihydro-1H-benzo[D][1,3]oxazine

Produkt 1

HCID 120431855-(2,4,4-Trimethyl-1,4-dihydro-2H-3,1-benzoxazin-6-yl)thiophene-2-carbonitrileAusbeute 25,1 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Katalysator2×HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

A mixture of 6-bromo-2,4,4-trimethyl-1,4-dihydro-2H-3,1-benzoxazine (3.6 g, 14 mmol), bis(pinacolato)diboron (5 g, 19.7 mmol), potassium acetate (4 g, 41 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]palladium (II) chloride (1:1 complex with methylene chloride, 0.4 g, 0.5 mmol) in DMF (80 ml,) was subject to a positive nitrogen flow to remove oxygen and then heated at 85° C. under a blanket of nitrogen for 18 hours. The mixture was allowed to cool to ambient temperature, treated with 5-bromo-2-thiophenecarbonitrile (4 g, 21 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium (II) chloride (1:1 complex with methylene chloride, 0.4 g, 0.5 mmol), and aqueous sodium carbonate solution (2M, 35 mL, 70 mmol), and then heated at 85° C. under nitrogen for 3 hours. The reaction mixture was allowed to cool to ambient temperature, brine (100 mL) and ethyl acetate (150 mL) were added. The organic layer was separated and aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organic layers were dried (MgSO4) and concentrated. The residue was purified by a flash silica gel column chromatography(THF:hexane/1:4) to afford the title compound as an off-white solid (1 g, 25%): mp 172-173° C.; 1H-NMR (DMSO-d6) δ 7.88 (d, 1H, J=4.0 Hz), 7.47 (d, 1H, J=4.0 Hz), 7.43 (d, 1H, J=2.0 Hz), 7.32 (dd, 1H, J=8.36, 2.4 Hz), 6.77 (s, 1H), 6.60 (d, 1H, J=8.4 Hz), 4.83 (m, 1H), 1.51 (s, 3H), 1.48 (s, 3H), 1.28 (d, 3H, J=5.6 Hz); MS (ESI) m/z 283 [M−H]−.

Aufarbeitung

  1. customto remove oxygen
  2. temperatureto cool to ambient temperature
  3. temperatureheated at 85° C. under nitrogen for 3 hours
  4. temperatureto cool to ambient temperature
  5. customThe organic layer was separated
  6. extractionaqueous layer was extracted with ethyl acetate (3×50 mL)
  7. dry with materialThe combined organic layers were dried (MgSO4)
  8. concentrationconcentrated
  9. customThe residue was purified by a flash silica gel column chromatography(THF:hexane/1:4)

Quellen und Nachweise

ORD-Eintrag
ord-b70aa4df65824c0d9167360b2c14fafd
Quelldatensatz
uspto-grants-2002_12
Patentnummer
US06498154B1

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