Sodium Carbonate → HCID 58827084, Verbindung

HRID 923251Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 923251
Br[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[CH:10]1[N:14]2[CH:15]=[N:16][CH:17]=[C:13]2[CH2:12][CH2:11]1)[C:5]#[N:6].[CH3:18]B1OB(C)OB(C)O1.C([O-])([O-])=O.[Na+].[Na+].[OH-].[K+]>COCCOC.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>[CH:17]1[N:16]=[CH:15][N:14]2[CH:10]([C:9]3[CH:8]=[CH:7][C:4]([C:5]#[N:6])=[CH:3][C:2]=3[CH3:18])[CH2:11][CH2:12][C:13]=12

Komponenten

7

Edukt 4

HCID 10340Sodium CarbonateHCID 14797Potassium HydroxideHCID 574072TrimethylboroxineHCID 588270573-bromo-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)benzonitrile

Produkt 1

HCID 58827084HCID 58827084, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

To a solution of 3-bromo-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)benzonitrile (0.100 g, 0.347 mmol) given in Example 3 (table 2) and trimethylboroxine (0.145 g, 1.04 mmol) in DME (3 mL); aqueous solutions of Na2CO3 (0.69 mL, 2 M) and KOH (0.17 mL, 2 M) are added. After degassing with nitrogen, Pd(PPh3)4 (0.040 g, 0.035 mmol) is added. The mixture is heated in a microwave reactor at 130° C. 1.5 h. At that point LCMS showed consumption of the starting material. The solution is diluted with ethyl acetate and saturated sodium bicarbonate. The resulting aqueous layer is extracted further with ethyl acetate (3×). The combined organic layers are washed with brine and dried over anhydrous sodium sulfate. After concentration the crude product is filtered through 0.45 μm filter and then purified by preparative HPLC (0% for 5 minutes and 0-34% acetonitrile with 0.1% TFA in 17 minutes). MS (ESI) m/z 224.0 (M+H); 1H NMR (400 MHz, CDCl3) δ ppm 2.33-2.42 (m, 1H), 2.43 (s, 3H), 2.84-2.95 (m, 2H), 3.07-3.18 (m, 1H), 5.54 (dd, J=8.1, 4.8 Hz, 1H), 6.65 (d, J=8.1 Hz, 1H), 6.83 (s, 1H), 7.32 (s, 1H), 7.41 (d, J=8.1 Hz, 1H), 7.50 (s, 1H). Resolution of the (R) and (S) enantiomers of the title compound is achieved by chiral HPLC using ChiralPak AS-H column and 9:1 hexane/EtOH to give enantiomer A (tr=84 min) and enantiomer B=104 min).

Aufarbeitung

  1. additionis added
  2. custom1.5 h
  3. customconsumption of the starting material
  4. additionThe solution is diluted with ethyl acetate and saturated sodium bicarbonate
  5. extractionThe resulting aqueous layer is extracted further with ethyl acetate (3×)
  6. washThe combined organic layers are washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationAfter concentration the crude product
  9. filtrationis filtered through 0.45 μm
  10. filtrationfilter
  11. custompurified by preparative HPLC (0% for 5 minutes and 0-34% acetonitrile with 0.1% TFA in 17 minutes)
  12. customto give enantiomer A (tr=84 min) and enantiomer B=104 min)

Quellen und Nachweise

ORD-Eintrag
ord-19179a712db0412d9b036b9619e47fba
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09278969B2

Notizen zur Reaktion

Wird geladen…