Cesium carbonate → HCID 68183109, compound

HRID 1615528Notes

Reaction equation

HRID 1615528 reaction equation
Br[C:2]1[S:6][C:5]2[C:7](=[O:19])[C:8]([CH3:18])([CH3:17])[CH:9]([C:10]3[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=3)[C:4]=2[CH:3]=1.[N:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.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]>[Cl:16][C:13]1[CH:14]=[CH:15][C:10]([CH:9]2[C:4]3[CH:3]=[C:2]([C:23]4[CH:24]=[CH:25][N:20]=[CH:21][CH:22]=4)[S:6][C:5]=3[C:7](=[O:19])[C:8]2([CH3:18])[CH3:17])=[CH:11][CH:12]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 68182963HCID 68182963, compound

Product 1

HCID 68183109HCID 68183109, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a 20 mL vial was added a solution of 2-bromo-4-(4-chlorophenyl)-5,5-dimethyl-4,5-dihydro-6H-cyclopenta[b]thiophen-6-one (0.0434 g, 0.122 mmol) and pyridine-4-boronic acid (0.02802 g, 0.2280 mmol) in 1,4-dioxane (2 mL) and water (0.200 mL). Cesium carbonate (0.1193 g, 0.3661 mmol) was added followed by [1,1′-bis(diphenylphosphino)ferrocene]palladium(II)dichloride (0.0120 g, 0.0146 mmol). The reaction mixture was heated to 90° C. and allowed to stir for 18 hr. The reaction was cooled to ambient temperature and quenched by the addition of a saturated aqueous solution of sodium bicarbonate (10 mL) and extracted with EtOAc (10 mL×3). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified and the enantiomers were separated on a Chiralpak IC 20×250 column using 90/10/01% Hexane/EtOH/DEA, 1.0 mL/minute for 40 minutes. Peak 1 RT=23.9 minutes (0.0050 g, 11%) and Peak 2 RT=39.4 minutes (0.0048 g, 11%) were both isolated as white solids. Absolute configuration of the obtained enantiomers is unknown. LC/MS (AA) ES+ 354, 356, 357, 358. 1H NMR (DMSO-d6, 400 MHz): δ 8.67-8.65 (2H, m), 7.88 (1H, s), 7.80-7.79 (2H, m), 7.43-7.42 (2H, m), 7.16-7.14 (2H, m), 4.48 (1H, s), 1.34 (3H, s), 0.63 (3H, s).

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. customquenched by the addition of a saturated aqueous solution of sodium bicarbonate (10 mL)
  3. extractionextracted with EtOAc (10 mL×3)
  4. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified
  8. customthe enantiomers were separated on a Chiralpak IC 20×250 column
  9. customfor 40 minutes
  10. customboth isolated as white solids

Sources & evidence

ORD record
ord-fb63cc7311d6493297e95bc26e3a4ab3
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

Loading…