4-Bromophenol → HCID 67248630, compound

HRID 84302Notes

Reaction equation

HRID 84302 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[CH3:9][O:10][C:11]1[N:16]=[CH:15][C:14]([CH2:17]O)=[CH:13][CH:12]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:17][C:14]2[CH:13]=[CH:12][C:11]([O:10][CH3:9])=[N:16][CH:15]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 78084-BromophenolHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 12259941(6-Methoxypyridin-3-yl)methanol

Product 1

HCID 67248630HCID 67248630, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

4-Bromophenol (1.37 g, 7.90 mmol) was added to a solution of (6-methoxypyridin-3-yl)methanol (1.0 g, 7.16 mmol) in THF (100 mL). Triphenylphosphine (1.88 g, 7.19 mmol) was added followed by triethylamine (0.727 g, 7.19 mmol). The resulting solution was cooled to 0° C. and DIAD (1.45 g, 7.19 mmol) was added by drop-wise addition and was maintained at 0° C. for 30 minutes, then warmed to room temperature and stirred for two days. The reaction was quenched by addition of water and extracted with ether (2×100 mL). The organic layer was washed with water (2×100 mL) then brine (1×100 mL), dried (MgSO4), filtered and concentrated to give a yellow oil. The crude material was purified by flash column chromatography on a Biotage SNAP cartridge Kp-sil 100g column (hexanes/ethyl acetate 9:1) to give a white solid. Mass/Yield—1.78 g/84% TLC (hexanes/ethyl acetate=8:2) Rf=0.12, UV active. LCMS MS ES+294.4/296.4. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.93 (s, 3 H) 4.93 (s, 2 H) 6.72-6.78 (m, 1 H) 6.81-6.86 (m, 2 H) 7.33-7.42 (m, 2 H) 7.58-7.65 (m, 1 H) 8.18 (s, 1 H).

Workup

  1. temperaturewas maintained at 0° C. for 30 minutes
  2. temperaturewarmed to room temperature
  3. customThe reaction was quenched by addition of water
  4. extractionextracted with ether (2×100 mL)
  5. washThe organic layer was washed with water (2×100 mL)
  6. dry with materialbrine (1×100 mL), dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a yellow oil
  10. customThe crude material was purified by flash column chromatography on a Biotage SNAP cartridge Kp-sil 100g column (hexanes/ethyl acetate 9:1)
  11. customto give a white solid

Sources & evidence

ORD record
ord-6cf446340a5f4bda8c5c261e9755c5d0
Source dataset
uspto-grants-2014_09
Patent number
US08846933B2

Reaction notes

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