Toluene → 4-(2-Methoxy-quinolin-5-yl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1373642Notes

Reaction equation

HRID 1373642 reaction equation
C1(C)C=CC=CC=1.Br[C:9]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:10]=1[CH:11]=[CH:12][C:13]([O:19][CH3:20])=[N:14]2.[C:21]([N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22].CC([O-])(C)C.[Na+]>C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1>[C:24]([O:23][C:21]([N:28]1[CH2:33][CH2:32][N:31]([C:9]2[CH:18]=[CH:17][CH:16]=[C:15]3[C:10]=2[CH:11]=[CH:12][C:13]([O:19][CH3:20])=[N:14]3)[CH2:30][CH2:29]1)=[O:22])([CH3:27])([CH3:25])[CH3:26]

Participants

8

Reactant 4

HCID 1140TolueneHCID 143452tert-Butyl piperazine-1-carboxylateHCID 142209695-Bromo-2-methoxyquinolineHCID 23676156Sodium t-butoxide

Product 1

HCID 694222494-(2-Methoxy-quinolin-5-yl)-piperazine-1-carboxylic acid tert-butyl esterYield 66%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 27342162-(Dicyclohexylphosphino)biphenylCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A third intermediate compound, 2-Methoxy-5-piperazin-1-yl-quinoline, was produced as follows: To an oven-dried flask, under nitrogen, was added Pd(OAc)2 (0.03 g, 0.13 mmol) and 2-(dicyclohexylphosphino)biphenyl (0.045 g, 0.13 mmol). The flask was evacuated and refilled with nitrogen. The following materials were added in the following order: degassed toluene (10 mL), 5-bromo-2-methoxy-quinoline (0.76 g, 3.23 mmol), 1-Boc-piperazine (0.72 g, 3.87 mmol), and NaOtBu (0.43 g, 4.52 mmol). The mixture was stirred at 80° C. for 1.5 h. After cooling to room temperature, the mixture was diluted with ethyl acetate and filtered through celite. The filtrate was concentrated in vaccuo and purified by chromatography on silica gel (10% EtOAc/Hexane) to give 4-(2-methoxy-quinolin-5-yl)-piperazine-1-carboxylic acid tert-butyl ester as a yellowish solid (0.73 g, 66%). 1H NMR (400 MHz, CDCl3) δ: 8.35 (d, 1H), 7.60 (m, 2H), 7.00 (d, 1H), 6.90 (d, 1H), 4.05 (s, 3H), 3.75 (m, 4H), 3.00 (m, 4H), 1.50 (s, 9H).

Workup

  1. customThe flask was evacuated
  2. additionrefilled with nitrogen
  3. additionThe following materials were added in the following order
  4. temperatureAfter cooling to room temperature
  5. filtrationfiltered through celite
  6. concentrationThe filtrate was concentrated in vaccuo
  7. custompurified by chromatography on silica gel (10% EtOAc/Hexane)

Sources & evidence

ORD record
ord-464fc088001c4c3fb4669856f3448c1f
Source dataset
uspto-grants-2007_01
Patent number
US07160888B2

Reaction notes

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