Ammonium Chloride → HCID 71008574, compound

HRID 1025607Notes

Reaction equation

HRID 1025607 reaction equation
[N:1]1([CH2:5][C:6]([CH3:16])([CH3:15])[O:7][C:8]2[CH:9]=[CH:10][C:11](Cl)=[N:12][CH:13]=2)[CH2:4][CH2:3][CH2:2]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.C[Si]([N-:46][Si](C)(C)C)(C)C.[Li+].[Cl-].[NH4+]>O1CCCC1.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]>[N:1]1([CH2:5][C:6]([CH3:16])([CH3:15])[O:7][C:8]2[CH:9]=[CH:10][C:11]([NH2:46])=[N:12][CH:13]=2)[CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 71739075HCID 71739075, compound

Product 1

HCID 71008574HCID 71008574, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
75 °C

Procedure

To a degassed solution of 5-(2-azetidin-1-yl-1,1-dimethyl-ethoxy)-2-chloro-pyridin (21.2 g, 88.1 mmol) in anhydrous tetrahydrofuran (314 ml) was added 2-(dicyclohexylphosphino)biphenyl (6.17 g, 17.6 mmol) and tris(dibenzylideneacetone)dipalladium(0) (8.06 g, 8.81 mmol). Then a solution of 1 M lithium bis(trimethylsilyl)amide in THF (264 ml, 264 mmol) was added via addition funnel over 5 minutes. The reaction mixture was stirred under argon atmosphere at 75° C. over-night. The reaction mixture was poured into a saturated solution of aqueous ammonium chloride (400 ml) and extracted with ethyl acetate (350 ml). The organic phase was collected and washed with 50% diluted brine (350 ml). The organic phase was collected and the aqueous phases were back extracted with ethyl acetate (2×200 ml). The combined organics were dried from magnesium sulfate, filtered and stripped. The remainder was purified by Analogix flash column chromatography (80 g column), eluting with 0% to 12% methanol in dichloromethane to provide the desired 5-(2-azetidin-1-yl-1,1-dimethyl-ethoxy)-pyridin-2-ylamine (10.59 g) as a dark brown semi-viscous oil (as well as a less-pure fraction which could be re-purified under similar conditions to provide another 4.01 g of product). LC/MS calc'd for C12H19N3O (m/e) 221.3, obs'd 222 (M+H, ES+).

Workup

  1. extractionextracted with ethyl acetate (350 ml)
  2. customThe organic phase was collected
  3. washwashed with 50% diluted brine (350 ml)
  4. customThe organic phase was collected
  5. extractionthe aqueous phases were back extracted with ethyl acetate (2×200 ml)
  6. dry with materialThe combined organics were dried from magnesium sulfate
  7. filtrationfiltered
  8. customThe remainder was purified by Analogix flash column chromatography (80 g column)
  9. washeluting with 0% to 12% methanol in dichloromethane

Sources & evidence

ORD record
ord-d28ca598522a45c7a0eeb2b01fa08945
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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