Tris(1,1-dimethylethyl)phosphine → HCID 68508241, compound

HRID 2189986Notes

Reaction equation

HRID 2189986 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][CH:19]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.[Li].C[Si]([N-][Si](C)(C)C)(C)C>C1(C)C=CC=CC=1>[CH2:25]([O:24][C:22]([C:19]1([C:2]2[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=2)[CH2:20][CH2:21][N:16]([C:14]([O:13][C:9]([CH3:10])([CH3:12])[CH3:11])=[O:15])[CH2:17][CH2:18]1)=[O:23])[CH3:26]

Participants

6

Reactant 4

HCID 83681Tris(1,1-dimethylethyl)phosphineHCID 27588121-Tert-butyl 4-ethyl piperidine-1,4-dicarboxylateHCID 27831712-Bromo-5-fluoropyridineHCID 86605622Lithium bistrimethylsilylamide

Product 1

HCID 68508241HCID 68508241, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Under an inert atmosphere a 250 mL three necked round bottom flask (flame dried) with a magnetic stirring bar was charged with 4 g (22.7 mmol) 2-bromo-5-fluoropyridine, 11.7 g (45 mmol) ethyl 1-tert.-butyloxycarbonylpiperidine-4-carboxylate, 416 mg (0.04 mmol) tris(dibenzylideneacetone)palladium(0), 0.91 mL tri-tert-butylphosphine (1M in toluene) and 60 ml toluene. To the dark red solution, 50 mL lithium-bis-(trimethylsilyl)-amid (1M in hexane) was added dropwise during 1 h at 18 to 23° C. The dark brown reaction solution was stirred for 87 h at room temperature. The reaction was quenched with saturated aqueous NH4Cl-solution. The aqueous layer was separated and extracted once with 200 mL ethyl acetate. The organic layers were washed once with 150 mL brine, dried over Na2SO4, filtered off and concentrated under vacuum. The residue was purified on silica eluting with a gradient formed from heptane and TBME to yield after evaporation of the product fractions 4 g (50%) of the title compound as yellow viscous oil. MS ISP (m/e): 253.3 (M-Boc)/353.2 [(M+H)+].

Workup

  1. customThe reaction was quenched with saturated aqueous NH4Cl-solution
  2. customThe aqueous layer was separated
  3. extractionextracted once with 200 mL ethyl acetate
  4. washThe organic layers were washed once with 150 mL brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered off
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified on silica eluting with a gradient
  9. customformed from heptane and TBME
  10. customto yield
  11. customafter evaporation of the product fractions 4 g (50%) of the title compound as yellow viscous oil

Sources & evidence

ORD record
ord-555a48a759894d999dab4f0b368840ff
Source dataset
uspto-grants-2012_12
Patent number
US08324250B2

Reaction notes

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