Sodium Iodide → 1-[3-(4-Butylpiperidin-1-yl)propyl]-6,7-difluoro-3,4-dihydro-1H-quinolin-2-one

HRID 2102618Notes

Reaction equation

HRID 2102618 reaction equation
Cl[CH2:2][CH2:3][CH2:4][N:5]1[C:14]2[C:9](=[CH:10][C:11]([F:16])=[C:12]([F:15])[CH:13]=2)[CH2:8][CH2:7][C:6]1=[O:17].[CH2:18]([CH:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)[CH2:19][CH2:20][CH3:21].[Na+].[I-].C([O-])([O-])=O.[K+].[K+]>CC#N>[CH2:18]([CH:22]1[CH2:27][CH2:26][N:25]([CH2:2][CH2:3][CH2:4][N:5]2[C:14]3[C:9](=[CH:10][C:11]([F:16])=[C:12]([F:15])[CH:13]=3)[CH2:8][CH2:7][C:6]2=[O:17])[CH2:24][CH2:23]1)[CH2:19][CH2:20][CH3:21]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 132838674-ButylpiperidineHCID 179561691-(3-Chloropropyl)-6,7-difluoro-3,4-dihydro-1H-quinolin-2-one

Product 1

HCID 179561811-[3-(4-Butylpiperidin-1-yl)propyl]-6,7-difluoro-3,4-dihydro-1H-quinolin-2-oneYield 57%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A 4 mL vial was charged with 1-(3-chloropropyl)-6,7-difluoro-3,4-dihydro-1H-quinolin-2-one (112KK03) (0.123 g, 0.47 mmol), 4-butylpiperidine (0.074 g, 0.52 mmol), NaI (0.100 g, 0.67 mmol), and K2CO3 (0.075 g, 0.54 mmol) in MeCN (2 mL) and shaken at 50° for 20 h. The reaction mixture was quenched with water, and the product extracted into EtOAc. The combined organic layers were purified by cation exchange CC followed by purification by flash CC (SiO2; MeOH/DCM 1:10) to give the title compound (112KK07) (0.097 g, 57%). 1H NMR (CD3OD) δ 7.20-7.09 (m, 2H), 3.91 (t, J=7.2 Hz, CH2), 2.90-2.82 (m, 4H), 2.59-2.55 (m, 2H), 2.38-2.34 (m, 2H), 1.97-1.91 (m, 2H), 1.82-1.75 (m, 2H), 1.66 (d, J=9.8 Hz, 2H), 1.28-1.16 (m, 9H), 0.87 (t, J=6.7 Hz, CH3); 13C NMR (CD3OD) δ 172.1, 150.4 (q, J=243.2 Hz, J=13.2 Hz), 146.9 (q, J=243.2 Hz, J=12.6 Hz), 137.3 (q, J=8.1 Hz, J=2.9 Hz), 124.9 (q, J=5.8 Hz, J=3.9 Hz), 117.6 (d, J=18.7 Hz), 106.4 (d, J=22.6 Hz), 56.8, 55.0, 41.8, 37.4, 36.8, 33.1, 32.4, 30.1, 25.5, 25.3, 23.9, 14.4.

Workup

  1. customThe reaction mixture was quenched with water
  2. extractionthe product extracted into EtOAc
  3. customThe combined organic layers were purified by cation exchange CC
  4. customfollowed by purification by flash CC (SiO2; MeOH/DCM 1:10)

Sources & evidence

ORD record
ord-c54e90dab7e14de6bad0080ac20d7170
Source dataset
uspto-grants-2009_08
Patent number
US07576078B2

Reaction notes

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