Tributylphosphine → Ethyl [(4-{[1-(6-bromo-2-pyridinyl)pentyl]oxy}-2-methylphenyl)oxy]acetate

HRID 1391758Notes

Reaction equation

HRID 1391758 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([CH:8]([OH:13])[CH2:9][CH2:10][CH2:11][CH3:12])[CH:5]=[CH:4][CH:3]=1.O[C:15]1[CH:27]=[CH:26][C:18]([O:19][CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])=[C:17]([CH3:28])[CH:16]=1.C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1.P(CCCC)(CCCC)CCCC>C1COCC1>[Br:1][C:2]1[N:7]=[C:6]([CH:8]([O:13][C:15]2[CH:27]=[CH:26][C:18]([O:19][CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])=[C:17]([CH3:28])[CH:16]=2)[CH2:9][CH2:10][CH2:11][CH3:12])[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 21986458Ethyl (4-hydroxy-2-methylphenoxy)acetateHCID 586299071-(6-Bromo-2-pyridinyl)-1-pentanol

Product 1

HCID 58629811Ethyl [(4-{[1-(6-bromo-2-pyridinyl)pentyl]oxy}-2-methylphenyl)oxy]acetateYield 64.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 1-(6-bromo-2-pyridinyl)-1-pentanol (2.00 g, 8.19 mmol) and ethyl (4-hydroxy-2-methylphenoxy)acetate (1.89 g, 8.99 mmol) in dry THF (160 mL) at 0° C. (ice/water bath) under nitrogen was added ADDP (4.13 g, 16.37 mmol) portion-wise over 5 min followed by nBu3P (1.07 mL, 4.30 mmol) drop-wise over 1-2 min. The mixture was stirred with slow warming to rt over 21 h and then concentrated under vacuum, diluted with EtOAc (300 mL) and washed with water (200 mL). The aqueous layer was then re-extracted with EtOAc (300 mL) and the combined organic layer washed with brine (350 mL), dried (MgSO4), filtered and reduced to give a orange solid residue. Purification by SPE (silica, 20 g Cartridge) eluting with cyclohexane:EtOAc (gradient 1:0 to 1:1) afforded the title compound (2.31 g).

Workup

  1. concentrationconcentrated under vacuum
  2. additiondiluted with EtOAc (300 mL)
  3. washwashed with water (200 mL)
  4. extractionThe aqueous layer was then re-extracted with EtOAc (300 mL)
  5. washthe combined organic layer washed with brine (350 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customto give a orange solid residue
  9. customPurification by SPE (silica, 20 g Cartridge)
  10. washeluting with cyclohexane

Sources & evidence

ORD record
ord-69159405f1824479833281941a6e5b92
Source dataset
uspto-grants-2008_03
Patent number
US07338960B2

Reaction notes

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