Ammonium Chloride → HCID 69085942, compound

HRID 1023466Notes

Reaction equation

HRID 1023466 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]2[CH2:12][CH2:11][CH2:10][CH:9]2[C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[CH:5]=[CH:4][N:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.[Li+].C[Si]([N-:50][Si](C)(C)C)(C)C.[NH4+].[Cl-]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[F:19][C:16]1[CH:17]=[CH:18][C:13]([CH:9]2[CH2:10][CH2:11][CH2:12][N:8]2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH2:50])[CH:7]=2)=[CH:14][CH:15]=1

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium Hexamethyldisilazide2×HCID 27342162-(Dicyclohexylphosphino)biphenylHCID 86673615HCID 86673615, compound

Product 1

HCID 69085942HCID 69085942, compoundYield 67.7%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

2-Chloro-4-[2-(4-fluoro-phenyl)-pyrrolidin-1-yl]-pyridine (97 mg, 0.35 mmol), tris(dibenzylideneacetone)dipalladium(0) (32 mg, 0.035 mmol) and 2-(dicyclohexylphosphino)biphenyl (25 mg, 0.070 mmol) are mixed in dry THF (2.0 mL). Then Argon is bubbled through the solution for 5 min and 1.0 M LiHMDS (0.53 mL, 0.53 mmol) is added. Then the reaction mixture is heated at 65° C. for 6 hrs before more 1.0 M LiHMDS (0.53 mL, 0.53 mmol) is added. The resulting mixture is heated at 65° C. for another 16 hrs. Then saturated NH4Cl aqueous solution (20 mL) is added along with water (25 mL). The mixture is extracted with EtOAc (3×50 mL) and the organic layers are combined and concentrated to give the crude product. Purification by silica flash column chromatography using MeOH in DCM (gradient from 0% to 10%) followed by Gilson preparative HPLC affords 61 mg of desired product.

Workup

  1. customThen Argon is bubbled through the solution for 5 min
  2. additionis added
  3. extractionThe mixture is extracted with EtOAc (3×50 mL)
  4. concentrationconcentrated
  5. customto give the crude product
  6. customPurification by silica flash column chromatography

Sources & evidence

ORD record
ord-e4a9343cfa5c4337b4cc1e71edce5217
Source dataset
uspto-grants-2014_05
Patent number
US08722709B2

Reaction notes

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