Potassium Carbonate → 6-Fluoro-1-[3-(4-propoxypiperidin-1-yl)propyl]-3,4-dihydro-1H-quinolin-2-one

HRID 969408Notes

Reaction equation

HRID 969408 reaction equation
Cl[CH2:2][CH2:3][CH2:4][N:5]1[C:14]2[C:9](=[CH:10][C:11]([F:15])=[CH:12][CH:13]=2)[CH2:8][CH2:7][C:6]1=[O:16].[CH2:17]([O:20][CH:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1)[CH2:18][CH3:19].C([O-])([O-])=O.[K+].[K+]>CC#N>[F:15][C:11]1[CH:10]=[C:9]2[C:14](=[CH:13][CH:12]=1)[N:5]([CH2:4][CH2:3][CH2:2][N:24]1[CH2:25][CH2:26][CH:21]([O:20][CH2:17][CH2:18][CH3:19])[CH2:22][CH2:23]1)[C:6](=[O:16])[CH2:7][CH2:8]2

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 114920374-PropoxypiperidineHCID 179561031-(3-Chloropropyl)-6-fluoro-3,4-dihydro-1H-quinolin-2-one

Product 1

HCID 179561446-Fluoro-1-[3-(4-propoxypiperidin-1-yl)propyl]-3,4-dihydro-1H-quinolin-2-oneYield 47.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A 4 mL vial was charged with 1-(3-chloropropyl)-6-fluoro-3,4-dihydro-1H-quinolin-2-one (92LH79) (0.242 g, 1.00 mmol), 4-propoxypiperidine (0.143 g, 1.00 mmol), KI (0.250 g, 1.50 mmol), and K2CO3 (0.207 g, 1.50 mmol) in MeCN (2 mL) and shaken at 40° for 20 h. The reaction mixture was quenched with water, and the product extracted into EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated. The product was purified by flash CC (SiO2; EtOAc, MeOH/EtOAc 1:4) to give the title compound (107LH70) (0.165 g, 47%). 1H NMR (CD3OD) δ 7.19-7.15 (m, 1H), 7.01-6.97 (m, 2H), 3.96 (t, J=7.4 Hz, CH2), 3.40 (t, J=6.6 Hz, CH2), 3.35-3.30 (m, 3H), 2.88 (t, J=6.8 Hz, 2H), 2.76 (m, 2H), 2.60-2.57 (m, 2H), 2.43-2.39 (m, 2H), 2.22-2.17 (m, 2H), 1.90-1.78 (m, 4H), 1.61-1.50 (m, 4H), 0.91 (t, J=7.4 Hz, CH3); 13C NMR (CD3OD) δ 172.2, 160.0 (d, J=242.2 Hz), 136.7 (d, J=2.3 Hz), 130.6 (d, J=7.7 Hz), 117.8 (d, J=8.5 Hz), 115.9 (d, J=23.1 Hz), 114.64 (d, J=22.3 Hz), 75.6, 70.7, 56.5, 52.0, 41.6, 32.4, 31.8, 26.1, 25.5, 24.2, 11.0; HPLC-MS (ammonium acetate) [M+H+]=349.30.

Workup

  1. customThe reaction mixture was quenched with water
  2. extractionthe product extracted into EtOAc
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe product was purified by flash CC (SiO2; EtOAc, MeOH/EtOAc 1:4)

Sources & evidence

ORD record
ord-f2efb85a2869434e8e4feeffb3bfbc8c
Source dataset
uspto-grants-2007_12
Patent number
US07307075B2

Reaction notes

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