Water → HCID 16782057, compound

HRID 2103304Notes

Reaction equation

HRID 2103304 reaction equation
[H-].[Na+].[NH:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6][CH2:5][C:4]1=[O:13].Br[CH2:15][CH2:16][CH2:17][Cl:18].O>CN(C)C=O>[Cl:18][CH2:17][CH2:16][CH2:15][N:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6][CH2:5][C:4]1=[O:13]

Participants

6

Reactant 4

HCID 962WaterHCID 80061-Bromo-3-chloropropaneHCID 24758Sodium hydrideHCID 64796Hydrocarbostyril

Product 1

HCID 16782057HCID 16782057, compoundYield 79.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of NaH in mineral oil (55-60%) (712 mg) was added to a solution of 3,4-dihydro-1H-quinolin-2-one (2.0 g, 13.6 mmol) in N,N-dimethylformamide (50 mL) at 0° C. The reaction mixture was stirred at 0° C. for 1 h. then 1-bromo-3-chloropropane (1.34 mL, 13.6 mmol) was added. The slurry was stirred for additional 16 h. at ambient temperature then water (50 mL) was added and the product was extracted with diethyl ether (2×50 mL). The organic layer was dried (Na2SO4) and concentrated in vacuo. The product was purified by flash-chromatography (eluent: dichloromethane) to give 1-[3-chloropropyl]-3,4-dihydro-1H-quinolin-2-one (2.41 g, 10.8 mmol). KI (2.5 g, 15 mmol), K2CO3 (2.1 g, 15 mmol) and 4-butylpiperidine (1.8 mL, 15 mmol) were added to a solution of 1-[3-chloropropyl]-3,4-dihydro-1H-quinolin-2-one (2.41 g, 10.8 mmol) in acetonitrile (50 mL). The reaction mixture was stirred at 60° C. for 16 h. The acetonitrile was evaporated in vacuo, water (50 mL) was added and the product was extracted with ethyl acetate (2×50 mL). The organic layer was dried (Na2SO4), filtered and concentrated in vacuo. Purification by flash-chromatography (eluent: ethyl acetate) gave the title product. Yield: 2.06 g, 58%. Oxalate-salt was prepared from oxalic acid (1.1 eq.) in acetone. HPLC-MS: M+1+=329.5 (UV/MS(%)=100/100). 1H NMR (400 MHz, CD3OD): δ=0.89 (3H, t), 1.12-1.36 (9H, m), 1.67 (2H, broad d), 1.83 (2H, quin.), 1.97 (2H, broad t), 2.41 (2H, t), 2.59 (2H, t), 2.84-2.96 (4H, m), 3.99 (2H, t), 7.02 (1H, broad t), 7.16 (1H, broad d), 7.20 (1H, broad d), 7.25 (1H, broad t). 13C NMR (CD3OD): δ 13.2, 22.8, 24.3, 25.0, 28.9, 31.6, 31.9 (2C), 35.6, 36.2, 40.1, 53.8 (2C), 55.9, 115.2, 123.2, 127.0, 127.4, 127.9, 139.1, 171.5

Workup

  1. stirringThe slurry was stirred for additional 16 h. at ambient temperature
  2. extractionthe product was extracted with diethyl ether (2×50 mL)
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customThe product was purified by flash-chromatography (eluent: dichloromethane)

Sources & evidence

ORD record
ord-29b88de639a6456c8811ffc9170ec116
Source dataset
uspto-grants-2009_08
Patent number
US07576100B2

Reaction notes

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