Ethyl Acetate → HCID 10192816, compound

HRID 2222266Notes

Reaction equation

HRID 2222266 reaction equation
Br[C:2]1[CH:6]=[CH:5][N:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=2)[CH:3]=1.[Cl:13][C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1.C(=O)([O-])[O-].[K+].[K+].CCOC(C)=O>COCCOC.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>[Cl:13][C:14]1[CH:19]=[C:18]([C:2]2[CH:6]=[CH:5][N:4]([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=3)[CH:3]=2)[CH:17]=[CH:16][CH:15]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 2734323(3-Chlorophenyl)boronic acid2×HCID 534231772-(3-Bromo-1H-pyrrol-1-yl)pyridine

Product 1

HCID 10192816HCID 10192816, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
84 °C

Procedure

2-(3-Bromo-1H-pyrrol-1-yl)pyridine (1.34 g, 2 mmol), 3-chlorophenylboronic acid (0.62 g, 4 mmol), Pd(PPh3)4 (116 mg, 0.1 mmol) and potassium carbonate (560 mg, 4 mmol) were dissolved in a mixture of DME (18 mL) and H2O (2 mL) and degassed for 15 min with Ar (g). The reaction mixture was then heated at 84° C. for 18 h. At this time, a further 0.25 eq. of 3-chlorophenylboronic acid (0.16 g, 1 mmol) was added and heating was continued. After a total of 42 h, the reaction mixture was cooled to rt, H2O (40 mL) and EtOAc (40 mL) were added and the reaction mixture shaken, the EtOAc layer was separated and the aqueous layer shaken with EtOAc (2×30 mL). The combined organic layers were dried over Na2SO4 and concentrated to a yellow oil. This was purified by liquid chromatography on silica gel eluting with EtOAc:hexane (3:7) to afford a white solid that was further purified by preparative HPLC to afford 2-[3-(3-chlorophenyl)-1H-pyrrol-1-yl]pyridine as a white solid. 1H NMR (CD3Cl, 300 MHz) δ 8.52-8.54 (1H, m), 7.61 (1H, ddd), 7.35-7.37 (1H, m), 7.28 (1H, s), 7.15-7.24 (3H, m), 6.99 (1H, ddd), 6.86 (1H, d), 6.47-6.48 (1H, m), 6.41 (1H, dd).). MS (ESI) 255 (M+H)+.

Workup

  1. customdegassed for 15 min with Ar (g)
  2. temperatureheating
  3. temperatureAfter a total of 42 h, the reaction mixture was cooled to rt
  4. customthe EtOAc layer was separated
  5. stirringthe aqueous layer shaken with EtOAc (2×30 mL)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. concentrationconcentrated to a yellow oil
  8. customThis was purified by liquid chromatography on silica gel eluting with EtOAc:hexane (3:7)
  9. customto afford a white solid
  10. customthat was further purified by preparative HPLC

Sources & evidence

ORD record
ord-01813f34ecad439b99c9189ab9649962
Source dataset
uspto-grants-2008_05
Patent number
US07371767B2

Reaction notes

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