Sodium hydride → 4-(Benzyloxycarbonyl)-1-(4-chloroquinolin-7-ylmethyl)-piperazin-2-one

HRID 1432931Notes

Reaction equation

HRID 1432931 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][NH:14][C:13](=[O:17])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[I-].[H-].[Na+].Br[CH2:22][C:23]1[CH:32]=[C:31]2[C:26]([C:27]([Cl:33])=[CH:28][CH:29]=[N:30]2)=[CH:25][CH:24]=1>C1COCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([CH2:22][C:23]2[CH:32]=[C:31]3[C:26]([C:27]([Cl:33])=[CH:28][CH:29]=[N:30]3)=[CH:25][CH:24]=2)[C:13](=[O:17])[CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 30165Iodide IonHCID 736777Benzyl 3-oxopiperazine-1-carboxylateHCID 217084447-Bromomethyl-4-chloroquinoline

Product 1

HCID 179852514-(Benzyloxycarbonyl)-1-(4-chloroquinolin-7-ylmethyl)-piperazin-2-oneYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

4-(Benzyloxycarbonyl)-piperazin-2-one (1.1 g, 4.6 mmol) is dissolved in THF (50 mL), cooled in an ice bath and treated with tretrabutylammonium iodide (0.18 g, mmol) and 60% sodium hydride (0.24 g, 6.0 mmol). The reaction mixture is stirred at 0° C. for 30 minutes then treated dropwise with a solution of 7-bromomethyl-4-chloroquinoline (1.2 g, 4.6 mmol), Example 14, in THF (50 mL). The resulting solution is stirred at 0° C. for 2 h then quenched with ammonium chloride solution and concentrated. Dilution with ethyl acetate is followed by a water wash; the organic layer is dried (sodium sulfate) and concentrated. The residue is chromatographed (4% methanol/methylene chloride) to yield solid 4-(benzyloxycarbonyl)-1-(4-chloroquinolin-7-ylmethyl)-piperazin-2-one (1.2 g, 2.9 mmol). A portion of this material (0.75 g, 1.8 mmol) is dissolved in acetonitrile (20 mL) and treated with iodo trimethylsilane (0.78 mL, 5.4 mmol) at room temperature for 3 hours. The reaction is quenched with methanol and concentrated to dryness. Methanol addition and concentration is repeated four times. The final residue is taken up is 2M aqueous HCl; the solution is washed with ether and concentrated. The residue is recrystallized from isopropanol and ether to yield the title compound (0.63 g, 2.3 mmol) MS m/z: M+=275; 1HNMR (CD3OD, 300 MHz) δ9.1 (d, 1H), 8.5 (d, 1H), 8.2-8.3 (m, 2H), 8.0 (d, 1H), 5.2 (s, 2H), 4.1 (s, 2H), 3.7-3.8 (m, 2H), 3.6-3.7 (m, 2H).

Workup

  1. temperaturecooled in an ice bath
  2. stirringThe resulting solution is stirred at 0° C. for 2 h
  3. customthen quenched with ammonium chloride solution
  4. concentrationconcentrated
  5. washwash
  6. dry with materialthe organic layer is dried (sodium sulfate)
  7. concentrationconcentrated
  8. customThe residue is chromatographed (4% methanol/methylene chloride)

Sources & evidence

ORD record
ord-8b7ed72eee874eb9ada7c1a5bc93a63e
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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