Water → HCID 69420021, compound

HRID 1373641Notes

Reaction equation

HRID 1373641 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:23]=[CH:22][CH:21]=[C:20]3[C:15]=2[CH2:16][CH2:17][CH2:18][NH:19]3)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].I[CH3:27].O>C1COCC1.CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:23]=[CH:22][CH:21]=[C:20]3[C:15]=2[CH2:16][CH2:17][CH2:18][N:19]3[CH3:27])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 69417571HCID 69417571, compound

Product 1

HCID 69420021HCID 69420021, compoundYield 66.2%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

An intermediate compound, 1-Methyl-5-piperazin-1-yl-1,2,3,4-tetrahydro-quinoline, was produced as follows: To a stirred solution of 4-(1,2,3,4-tetrahydro-quinolin-5-yl)-piperazine-1-carboxylic acid tert-butyl ester (1.30 g, 4.10 mmol) in THF-DMF (1:1, 40 mL) was added NaH (60% dispersion in oil, 0.58 g, 24.16 mmol) at room temperature. The resulting mixture was stirred at room temperature for 1 h, cooled to 0° C. and iodomethane (1.75 g, 12.30 mmol) was added. The mixture was stirred at room temperature overnight and diluted with ethyl acetate. Water was added and the organic layer was separated. The aqueous layer was extracted with ethyl acetate. The combined organic extracts were washed with water, brine, dried (Na2SO4) and the solvent was removed in vacuo. The residue was purified on a silica gel column using hexanes-ethyl acetate (3:1) as eluent to give 4-(1-methyl-1,2,3,4-tetrahydro-quinolin-5-yl)-piperazine-1-carboxylic acid tert-butyl ester (0.90 g, 66%) as a liquid. 1H NMR (400 MHz, CDCl3): δ 7.10 (t, 1H), 6.40 (m, 2H), 3.50 (br s , 4H), 3.25 (t, 2H), 2.90 (s, 3H), 2.80 (br s, 4H), 2.75 (t, 2H), 1.90 (t, 3H), 1.45 (s, 9H).

Workup

  1. temperaturecooled to 0° C.
  2. stirringThe mixture was stirred at room temperature overnight
  3. customthe organic layer was separated
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. washThe combined organic extracts were washed with water, brine
  6. dry with materialdried (Na2SO4)
  7. customthe solvent was removed in vacuo
  8. customThe residue was purified on a silica gel column

Sources & evidence

ORD record
ord-146e482178e94f418c01bc6970407858
Source dataset
uspto-grants-2007_01
Patent number
US07160888B2

Reaction notes

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