Hydrochloric Acid → 2-(4-(4-Fluorophenyl)butyl)-nicotinic acid

HRID 1925529Notes

Reaction equation

HRID 1925529 reaction equation
[Li]CCCC.C(NC(C)C)(C)C.[CH3:13][C:14]1[N:22]=[CH:21][CH:20]=[CH:19][C:15]=1[C:16]([OH:18])=[O:17].Br[CH2:24][CH2:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=1.Cl>C1COCC1.O>[F:33][C:30]1[CH:31]=[CH:32][C:27]([CH2:26][CH2:25][CH2:24][CH2:13][C:14]2[N:22]=[CH:21][CH:20]=[CH:19][C:15]=2[C:16]([OH:18])=[O:17])=[CH:28][CH:29]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 6433732-Methylnicotinic acidHCID 147371331-(3-Bromopropyl)-4-fluorobenzeneHCID 178418339Butyllithium

Product 1

HCID 671339862-(4-(4-Fluorophenyl)butyl)-nicotinic acidYield 94%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-55 °C

Procedure

4.4 ml (11.0 mmol, 2.5M in hexane) of BuLi solution were added dropwise at −10° C. to a solution of 1.54 ml (11.0 mmol) of diisopropylamine in THF (10 ml). Stirring was then carried out for a further 30 min at −10° C. This solution was added dropwise at −75° C. to a solution of 685 mg (5.0 mmol) of 2-methyl-nicotinic acid in THF (2 ml). Stirring was then carried out for 30 min at −75° C. and for 60 min at 0° C., followed by cooling to −55° C. At that temperature, 1.62 g (7.5 mmol) of 1-(3-bromopropyl)-4-fluorobenzene were added and the reaction solution was stirred for 1 h at −55° C. After warming to RT and stirring for a further 16 h at RT, water (30 ml) and conc. hydrochloric acid (3 ml) were added. Extraction with EA (2×30 ml) was then carried out. The combined organic phases were dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by means of CC (EA), yielding 1.28 g (4.7 mmol, 93%) of 2-(4-(4-fluorophenyl)butyl)-nicotinic acid.

Workup

  1. stirringStirring
  2. waitwas then carried out for 30 min at −75° C. and for 60 min at 0° C.
  3. stirringthe reaction solution was stirred for 1 h at −55° C
  4. temperatureAfter warming to RT
  5. stirringstirring for a further 16 h at RT
  6. extractionExtraction with EA (2×30 ml)
  7. dry with materialThe combined organic phases were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by means of CC (EA)

Sources & evidence

ORD record
ord-50d7a001cce041ce924364e4002b749c
Source dataset
uspto-grants-2012_05
Patent number
US08178684B2

Reaction notes

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