2-Methyl-3-butyn-2-ol → HCID 56925648, compound

HRID 2175461Notes

Reaction equation

HRID 2175461 reaction equation
[CH3:1][C:2]([OH:6])([C:4]#[CH:5])[CH3:3].C1CCN2C(=NCCC2)CC1.C(OC(C(F)(F)F)=O)(C(F)(F)F)=O.[Br:31][C:32]1[CH:37]=[CH:36][C:35](O)=[CH:34][N:33]=1>C(#N)C>[Br:31][C:32]1[N:33]=[C:34]2[CH:5]=[CH:4][C:2]([CH3:3])([CH3:1])[O:6][C:35]2=[CH:36][CH:37]=1

Participants

6

Reactant 4

HCID 82582-Methyl-3-butyn-2-ol2×HCID 9845Trifluoroacetic anhydrideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene2×HCID 27628652-Bromo-5-hydroxypyridine

Product 1

HCID 56925648HCID 56925648, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a solution 2-methyl-3-butyn-2-ol (21) in acetonitrile (6 mL) was added DBU (0.80 mL, 6.61 mmol) at 0° C., then TFAA was added dropwise, also at 0° C. The reaction was stirred for 30 min. In another round bottom flask, DBU (0.80 mL, 6.61 mmol) was added to a solution of 2-bromo-5-hydroxy pyridine (1 g, 5.75 mmol) in 6 mL of acetonitrile at 0° C. Then 2-methyl-3-butyn-2-ol was added dropwise into this reaction, which was stirred for 30 additional min. The solvent was removed by rotary evaporation, and the residue was diluted with DCM. After separation, the organic layer was washed with 1M HCl, 1M NaOH, sat NaHCO3 and brine, was dried over MgSO4 and concentrated in vacuum. The crude product was dissolved in 2 ml of xylene and subjected to microwave irradiation (130° C., 220 W) for 30 min. The solvent was removed by rotary evaporation and the product concentrated in vacuum. The crude product was purified by column chromatography (silica gel) (10:1 Hx/EtOAc) to give 300 mg of a yellow solid (23% over the two steps). 1H NMR (CDCl3): 1.45 (s, 6H), 5.86 (d, 1H, J=10.4), 6.44 (d, 1H, J=10), 6.90 (d, 1H, J=8.8), 7.14 ppm (s, 1H, J=8.4). HRMS (ESI) m/z calcd for C10H11NOBr [(M+H)+] 240.0024. found: 240.0026.

Workup

  1. stirringwas stirred for 30 additional min
  2. customThe solvent was removed by rotary evaporation
  3. additionthe residue was diluted with DCM
  4. customAfter separation
  5. washthe organic layer was washed with 1M HCl, 1M NaOH
  6. dry with materialwas dried over MgSO4
  7. concentrationconcentrated in vacuum
  8. dissolutionThe crude product was dissolved in 2 ml of xylene
  9. customsubjected to microwave irradiation (130° C., 220 W) for 30 min
  10. customThe solvent was removed by rotary evaporation
  11. concentrationthe product concentrated in vacuum
  12. customThe crude product was purified by column chromatography (silica gel) (10:1 Hx/EtOAc)

Sources & evidence

ORD record
ord-6d6d8c33934f4f029eb71dc5ace83a0e
Source dataset
uspto-grants-2015_06
Patent number
US09062072B2

Reaction notes

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