Benzyl piperazine-1-carboxylate → Benzyl 4-(2-(benzyloxy)pyridin-3-yl)piperazine-1-carboxylate

HRID 1804619Notes

Reaction equation

HRID 1804619 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C(N(C)C)=CC=CC=2)CCCCC1.[CH2:29]([O:36][C:37]1[C:42](Br)=[CH:41][CH:40]=[CH:39][N:38]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[N:44]1([C:50]([O:52][CH2:53][C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)=[O:51])[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.O.C1(/C=C/C(=O)/C=C/C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH2:29]([O:36][C:37]1[C:42]([N:47]2[CH2:46][CH2:45][N:44]([C:50]([O:52][CH2:53][C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)=[O:51])[CH2:49][CH2:48]2)=[CH:41][CH:40]=[CH:39][N:38]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

8

Reactant 4

HCID 643495Benzyl piperazine-1-carboxylateHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 147124562-Benzyloxy-3-bromopyridineHCID 23676156Sodium t-butoxide

Product 1

HCID 67060675Benzyl 4-(2-(benzyloxy)pyridin-3-yl)piperazine-1-carboxylateYield 55%

Reagents, catalysts & solvents 3

HCID 15673654(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred suspension of 0.011 g (0.012 mmol) of (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one-palladium (3:2) in 3 mL of anhydrous toluene under an atmosphere of nitrogen was added 0.015 g (0.037 mmol) of 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine and the resulting mixture was allowed to stir for 20 min. Next, 0.11 g (0.41 mmol) of 2-(benzyloxy)-3-bromopyridine was added followed by 0.11 g (0.49 mmol) of benzyl piperazine-1-carboxylate and 0.059 g (0.61 mmol) of sodium tert-butoxide. The resulting mixture was then heated to 80° C. overnight. After cooling to ambient temperature, the reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with water then brine, dried over magnesium sulfate and evaporated to dryness in vacuo. The residue was purified by silica gel chromatography eluting with a 0-100% acetone in hexanes gradient to afford the title compound as clear gum (0.090 g, 55%). 1H-NMR (500 MHz, CDCl3) δ 7.84 (dd, J=4.9, 1.6 Hz, 1H), 7.47-7.29 (m, 10H), 7.09 (dd, J=7.5, 1.6 Hz, 1H), 6.87 (dd, J=7.5, 4.9 Hz, 1H), 5.46 (s, 2H), 5.16 (s, 2H), 3.67-3.65 (m, 4H), 3.07 (br s, 4H). LC-MS: m/z (ES) 404.0 (MH)+.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. extractionextracted with ethyl acetate
  3. washThe combined organic layers were washed with water
  4. dry with materialbrine, dried over magnesium sulfate
  5. customevaporated to dryness in vacuo
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with a 0-100% acetone in hexanes gradient

Sources & evidence

ORD record
ord-c69d606ce85b4564ae29aa1d539c9d58
Source dataset
uspto-grants-2013_01
Patent number
US08354403B2

Reaction notes

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