Triethylamine → 3-(4-BOC-piperazino)-2-chloropyridine

HRID 220441Notes

Reaction equation

HRID 220441 reaction equation
[Cl:1][C:2]1[C:7](I)=[CH:6][CH:5]=[CH:4][N:3]=1.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][N:19]([C:7]2[C:2]([Cl:1])=[N:3][CH:4]=[CH:5][CH:6]=2)[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 10796Cesium carbonateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 634876Binap, (A+-)-HCID 27357432-Chloro-3-iodopyridine

Product 1

HCID 593218363-(4-BOC-piperazino)-2-chloropyridineYield 54%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

Dissolve 2-chloro-3-iodopyridine (4.00 g, 16.74 mmol) in anhydrous toluene (25 mL). Add piperazine-1-carboxylic acid t-butyl ester (2.96 g, 15.90 mmol), followed by palladium acetate (0.113 g, 0.50 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.313 g, 0.502 mmol), triethylamine (0.034 g, 0.047 mL, 0.335 mmol) and cesium carbonate (27.3 g, 83.7 mmol). Heat at reflux for 18 hr. Concentrate and partition the residue between DCM and a saturated solution of sodium bicarbonate. Extract the aqueous phase twice with DCM and once with ethyl acetate. Dry the combined organic extracts (sodium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 5:95 to 20:80 ethyl acetate:hexanes), to give 4-(2-Chloropyridin-3-yl)-piperazine-1-carboxylic acid t-butyl ester (54%). MS (ES): m/z=298 [M+H].

Workup

  1. temperatureHeat
  2. temperatureat reflux for 18 hr
  3. concentrationConcentrate
  4. custompartition the residue between DCM
  5. extractionExtract the aqueous phase twice with DCM
  6. dry with materialDry the combined organic extracts (sodium sulfate)
  7. filtrationfilter
  8. concentrationconcentrate
  9. custompurify
  10. wash(silica gel chromatography, eluting with 5:95 to 20:80 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-a8066f2c014748939b38035db32aaae5
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

Loading…