Triethylamine → 2-Bromo-5-fluoro-4-isopropenyl-pyridine

HRID 474078Notes

Reaction equation

HRID 474078 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([C:8](O)([CH3:10])[CH3:9])[C:5]([F:12])=[CH:4][N:3]=1.CS(OS(C)(=O)=O)(=O)=O.C(N(CC)CC)C>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[C:6]([C:8]([CH3:10])=[CH2:9])[C:5]([F:12])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 8471Triethylamine2×HCID 81560Methanesulfonic anhydride2×HCID 866680482-Bromo-5-fluoro-alpha,alpha-dimethyl-4-pyridinemethanol

Product 1

HCID 866680492-Bromo-5-fluoro-4-isopropenyl-pyridine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(2-bromo-5-fluoro-pyridin-4-yl)-propan-2-ol (24.7 g, 106 mmol) and methanesulfonic anhydride (55.1 g, 317 mmol) in DCM (250 ml) was added triethylamine (58.8 ml, 42.7 g, 422 mmol). The reaction mixture was stirred at rt for 20 h. Another 1 eq. (18 g) of methanesulfonic anhydride and 1.2 eq. (17 ml) of triethylamine were added and the reaction mixture was stirred an additional 20 h at rt. The reaction mixture was quenched with 1M aq. Na2CO3 sol. and diluted with DCM. The phases were separated and the aq. phase was reextracted twice with DCM. The combined org. phases were washed with brine, dried over Na2SO4, filtered and concentrated. Flash chromatography on silica gel (hexane:EtOAc 8:1) yielded the title compound as a clear colourless liquid. HPLC RtH4=1.12 min; ESIMS: 216, 218 [(M+H)+]; 1H NMR (400 MHz, CDCl3): δ 8.20 (d, 1H), 7.40 (d, 1H), 5.48-5.44 (m, 2H), 2.14 (s, 3H).

Workup

  1. stirringthe reaction mixture was stirred an additional 20 h at rt
  2. customThe reaction mixture was quenched with 1M aq. Na2CO3 sol.
  3. additiondiluted with DCM
  4. customThe phases were separated
  5. washphases were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-da931ece6d4e4079ad2c8865da9d5678
Source dataset
uspto-grants-2014_01
Patent number
US08637508B2

Reaction notes

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