Acetic Acid → HCID 22607239, compound

HRID 2307802Notes

Reaction equation

HRID 2307802 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[N:15]=1.[Li+].CC([N-]C(C)C)C.[CH:29](=[O:36])[C:30]1[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=1.C(O)(=O)C>C1COCC1.CO.CCOC(C)=O>[F:13][C:14]1[C:19]([CH:29]([C:30]2[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=2)[OH:36])=[CH:18][CH:17]=[C:16]([F:20])[N:15]=1

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 7912DiisopropylamineHCID 133894-PyridinecarboxaldehydeHCID 739342,6-DifluoropyridineHCID 2724682Lithium diisopropylamideHCID 178418339Butyllithium

Product 1

HCID 22607239HCID 22607239, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 21584119Ethylacetate methanolSolvent

Procedure

To diisopropylamine (9.3 mL, 66.1 mmol) in THF (100 mL) at −78° C. was added n-BuLi (23.1 mL of a 2.5 M solution in hexanes, 57.8 mmol) dropwise via syringe. 2,6-difluoropyridine (5.0 mL, 55.1 mmol) in THF (100 mL) at −78° C. was added to the above prepared LDA solution dropwise via canula to give a clear yellow-green solution. isonicotinaldehyde (6.3 mL, 66.1 mmol) was added causing a white precipitate to form. The reaction mixture was warmed to room temperature and then glacial acetic acid (3.3 mL, 57.8 mmol) was added. Silica gel was added and the volatiles removed on a rotary evaporator. Flash chromatography (80-100% EtOAc/hexanes-3-5-7% MeOH/EtOAc) gave 8.48 g (69%) of as an off white solid. Rf=0.38 (5% MeOH/EtOAc); MS m/z 223 (M+H)+; 1H NMR (300 MHz, DMSO-D6) δ ppm 5.91 (d, J=4.41 Hz, 1 H) 6.49 (d, J=4.41 Hz, 1 H) 7.20 (dd, J=8.31, 2.54 Hz, 1 H) 7.36 (m, 2 H) 8.19 (m, 1 H) 8.53 (m, 2 H); Found: 223, 221; Anal calcd for C11H8F2N2O: C, 59.46; H, 3.63; N, 12.61. Found: C, 59.45; H, 3.66; N, 12.62.

Workup

  1. customto give a clear yellow-green solution
  2. customto form
  3. additionSilica gel was added
  4. customthe volatiles removed on a rotary evaporator
  5. customFlash chromatography (80-100% EtOAc/hexanes-3-5-7% MeOH/EtOAc) gave 8.48 g (69%) of as an off white solid

Sources & evidence

ORD record
ord-31dd3710d5eb4adab30de1b40c3dbe6c
Source dataset
uspto-grants-2004_12
Patent number
US06831175B2

Reaction notes

Loading…