Potassium Phosphate, Tribasic → 4-[2-(4-Fluorophenyl)-pyridin-3-yl]-piperazine-1-carboxylic acid t-butyl ester

HRID 220442Notes

Reaction equation

HRID 220442 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:15](Cl)=[N:16][CH:17]=[CH:18][CH:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].C1([C-]2C(C3C=CC=CC=3)=C(C3C=CC=CC=3)C(C3C=CC=CC=3)=C2C2C=CC=CC=2)C=CC=CC=1.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[Fe+2]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:15]([C:25]3[CH:26]=[CH:27][C:22]([F:21])=[CH:23][CH:24]=3)=[N:16][CH:17]=[CH:18][CH:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2856454-Fluorophenylboronic acidHCID 593218363-(4-BOC-piperazino)-2-chloropyridine

Product 1

HCID 687228274-[2-(4-Fluorophenyl)-pyridin-3-yl]-piperazine-1-carboxylic acid t-butyl esterYield 28%

Reagents, catalysts & solvents 3

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 129828017Ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane;iron(2+);(2,3,4,5-tetraphenylcyclopenta-1,4-dien-1-yl)benzeneCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Dissolve 4-(2-chloropyridin-3-yl)-piperazine-1-carboxylic acid t-butyl ester (2.7 g, 9.1 mmol) in toluene (30 mL). Add 4-fluorophenylboronic acid (1.92 g, 13.70 mmol) followed by bis(dibenzylideneacetone)palladium(0) (0.42 g, 0.46 mmol), 1,2,3,4,5-pentaphenyl-1′-(di-t-butylphosphino)ferrocene (CTC-Q-PHOS) (0.65 g, 0.91 mmol) and potassium phosphate (5.8 g, 27.3 mmol). Heat the reaction mixture at 100° C. for 23 hr. Cool to room temperature, concentrate and partition the residue between ethyl acetate and 1 N sodium hydroxide (pH=11). Dry (sodium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 20:80 ethyl acetate:hexanes), to give 4-[2-(4-fluorophenyl)-pyridin-3-yl]-piperazine-1-carboxylic acid t-butyl ester (28%). MS (ES): m/z=358 [M+H].

Workup

  1. temperatureCool to room temperature
  2. concentrationconcentrate
  3. custompartition the residue between ethyl acetate and 1 N sodium hydroxide (pH=11)
  4. dry with materialDry (sodium sulfate)
  5. filtrationfilter
  6. concentrationconcentrate
  7. custompurify
  8. wash(silica gel chromatography, eluting with 20:80 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-442e3914cfbc4e5b9d3a867ccfc19ef0
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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