Triphenylphosphine → tert-Butyl (2-((5-bromopyridin-3-yl)oxy)ethyl)carbamate

HRID 1774732Notes

Reaction equation

HRID 1774732 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[N:6][CH:7]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[CH2:29][CH2:30][NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35].C1C(COC(/N=N\C(OCC2C=CC(Cl)=CC=2)=O)=O)=CC=C(Cl)C=1.C([O-])(O)=O.[Na+]>C1COCC1.CCOC(C)=O>[C:34]([O:33][C:32](=[O:38])[NH:31][CH2:30][CH2:29][O:8][C:4]1[CH:5]=[N:6][CH:7]=[C:2]([Br:1])[CH:3]=1)([CH3:37])([CH3:36])[CH3:35]

Participants

8

Reactant 5

HCID 11776TriphenylphosphineHCID 516892Sodium BicarbonateHCID 5995293-Bromo-5-hydroxypyridineHCID 2733206tert-butyl N-(2-hydroxyethyl)carbamateHCID 16218364(4-chlorophenyl)methyl (NZ)-N-[(4-chlorophenyl)methoxycarbonylimino]carbamate

Product 1

HCID 71627051tert-Butyl (2-((5-bromopyridin-3-yl)oxy)ethyl)carbamateYield 63%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-bromopyridin-3-ol (0.5 g, 2.87 mmol) in THF (30 mL) cooled to 0° C. were added triphenylphosphine (0.829 g, 3.16 mmol) and tert-butyl 2-hydroxyethylcarbamate (0.51 g, 3.16 mmol) in THF (5 mL) followed by di-(4-chlorobenzyl)azodicarboxylate (1.16 g, 3.16 mmol), added portionwise, and the reaction mixture was then stirred at room temperature over night. The mixture was diluted with EtOAc, poured into aq. NaHCO3 (50 mL) and the aqueous layer was extracted with EtOAc (2×100 mL). Combined organics were washed with brine, dried over Na2SO4, filtered and evaporated. The residue was taken up in diethyl ether (50 mL) and left to stand in the fridge for 2 h. After this time, the solid precipitate was filtered off and the resulting filtrate evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 30% EtOAc-heptane gradient to give the title compound (0.57 g, 63%) as a white solid. MS: 317.0 and 319.0 (M+H+).

Workup

  1. additionadded portionwise
  2. extractionthe aqueous layer was extracted with EtOAc (2×100 mL)
  3. washCombined organics were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. waitleft
  8. filtrationAfter this time, the solid precipitate was filtered off
  9. customthe resulting filtrate evaporated to dryness
  10. customThe residue was purified by silica gel flash chromatography
  11. washeluting with a 0 to 30% EtOAc-heptane gradient

Sources & evidence

ORD record
ord-748fa926b8eb4ec6be88caec406fe14d
Source dataset
uspto-grants-2016_02
Patent number
US09260408B2

Reaction notes

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