Hydrochloric Acid → HCID 66742859, compound

HRID 449556Notes

Reaction equation

HRID 449556 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[CH2:12][CH:11]([O:13][CH3:14])[CH2:10]2)=[CH:4][N:3]=1.C1(C2C=CC=CC=2)C=CC=CC=1P(C1CCCCC1)C1CCCCC1.C[Si]([N-:44][Si](C)(C)C)(C)C.[Li+].Cl>C1COCC1.C(Cl)Cl.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].CCN(CC)CC.CO.C1(C)C=CC=CC=1>[CH3:14][O:13][CH:11]1[CH2:12][N:9]([CH2:8][C:5]2[CH:6]=[CH:7][C:2]([NH2:44])=[N:3][CH:4]=2)[CH2:10]1

Participants

11

Reactant 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 86662313HCID 86662313, compound

Product 1

HCID 66742859HCID 66742859, compound

Reagents, catalysts & solvents 6

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolvent2×HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

To a round bottomed flask charged with 2-chloro-5-((3-methoxyazetidin-1-yl)methyl)pyridine (11.5 g, 54.1 mmol, Eq: 1.00), tris(dibenzylideneacetone)dipalladium(0) (1.24 g, 1.35 mmol, Eq: 0.025), and biphenyl-2-yldicyclohexylphosphine (948 mg, 2.7 mmol, Eq: 0.05) was added toluene (150 ml) followed immediately by lithium bis(trimethylsilyl)amide (81.1 ml, 81.1 mmol, Eq: 1.5) as a 1.0 M solution in THF. Brought quickly to reflux and stirred overnight under Argon. Next day, the reaction was checked by TLC (9:1 MC:MeOH) and the starting material was gone, replaced primarily by a single lower Rf spot. Cooled while stirring and added 5 ml of 1.0M HCl. Stirred 20 min and filtered over celite. The filtrate was diluted with ether and washed with 200 mL of 1.0M NaOH followed by water and brine. Dried the org phase over sodium sulfate, filtered and removed solvent. Obtained a dark red oil weighing 14.4 g. Took the oil up in CH2Cl2 and flashed (neat MC to 90:10 MC:MeOH:0.1 Et3N). Collected 4.4 g (42.1%) of cleanest fractions as a reddish oil for next step.

Workup

  1. temperatureBrought quickly to reflux
  2. temperatureCooled
  3. stirringwhile stirring
  4. stirringStirred 20 min
  5. filtrationfiltered over celite
  6. additionThe filtrate was diluted with ether
  7. washwashed with 200 mL of 1.0M NaOH
  8. dry with materialDried the org phase over sodium sulfate
  9. filtrationfiltered
  10. customremoved solvent
  11. customObtained a dark red oil
  12. customCollected 4.4 g (42.1%) of cleanest fractions as a reddish oil for next step

Sources & evidence

ORD record
ord-5ef07489082841559d5d1f8d427125bd
Source dataset
uspto-grants-2013_07
Patent number
US08481540B2

Reaction notes

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