Sodium hydride → tert-Butyl {1-[2-(7-methoxy-4-oxoquinolin-1(4H)-yl)ethyl)piperidin-4-yl}carbamate

HRID 255164Notes

Reaction equation

HRID 255164 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7]([OH:13])=[CH:8][CH:9]=[N:10]2)=[CH:5][CH:4]=1.[H-].[Na+].CS(O[CH2:21][CH2:22][N:23]1[CH2:28][CH2:27][CH:26]([NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:25][CH2:24]1)(=O)=O.C(#N)C.O>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7](=[O:13])[CH:8]=[CH:9][N:10]2[CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][CH:26]([NH:29][C:30](=[O:31])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH2:25][CH2:24]2)=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 18373917Acetonitrile--water (1/1)HCID 568344782-(4-((Tert-butoxycarbonyl)amino)piperidin-1-yl)ethyl methanesulfonate2×HCID 178487715HCID 178487715, compound2×

Product 1

HCID 86642601tert-Butyl {1-[2-(7-methoxy-4-oxoquinolin-1(4H)-yl)ethyl)piperidin-4-yl}carbamateYield 33%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 7-methoxyquinolin-4-ol (Intermediate 10, 500 mg, 2.85 mmol) in dry DMF (10 mL) was treated at 0° C. with a cooling bath under stirring with sodium hydride (114 mg, 60% in oil, 2.85 mmol). The cooling bath was removed and the mixture was stirred for 30 minutes at room temperature. A solution of 2-{4-[(tert-butoxycarbonyl)amino]piperidin-1-yl}ethyl methanesulfonate in DMF (Intermediate 6, 0.58 mmol/mL, 5 mL, 2.9 mmol) was added and the resulting solution was stirred over night at room temperature. DMF was removed under reduced pressure, the residue was taken up in ethyl acetate (100 mL) and saturated aqueous sodium hydrogen carbonate solution (30 mL) and the aqueous phase was back extracted three times with ethyl acetate (3×70 mL). The combined organic phases were dried over sodium sulfate. Some starting 7-methoxyquinolin-4-ol was precipitated from dichloromethane (30 mL) with hexanes (20 mL) and removed by filtration. The filtrate was concentrated to dryness under reduced pressure. Chromatography of the residue on silica gel with acetonitrile/water (15:1 to 10:1) gave 373 mg (33% yield) of the product as a colorless solid, mp 207° C.

Workup

  1. customThe cooling bath was removed
  2. stirringthe resulting solution was stirred over night at room temperature
  3. customDMF was removed under reduced pressure
  4. extractionsaturated aqueous sodium hydrogen carbonate solution (30 mL) and the aqueous phase was back extracted three times with ethyl acetate (3×70 mL)
  5. dry with materialThe combined organic phases were dried over sodium sulfate
  6. customSome starting 7-methoxyquinolin-4-ol was precipitated from dichloromethane (30 mL) with hexanes (20 mL)
  7. customremoved by filtration
  8. concentrationThe filtrate was concentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-76cb0eb1a6f84a57b8564bf7fd4cc62f
Source dataset
uspto-grants-2011_01
Patent number
US07875715B2

Reaction notes

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