1-Bromo-3-chloropropane → HCID 17956184, compound

HRID 2102631Notes

Reaction equation

HRID 2102631 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH:6]=[CH:5]2.[H-].[Na+].Br[CH2:16][CH2:17][CH2:18]Cl.C([O-])([O-])=O.[K+].[K+].[CH2:26]([CH:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1)[CH2:27][CH2:28][CH3:29]>CC#N.O.CCOC(C)=O.C(OCC)C.CN(C=O)C>[CH2:26]([CH:30]1[CH2:35][CH2:34][N:33]([CH2:16][CH2:17][CH2:18][N:8]2[C:9]3[C:4](=[CH:3][C:2]([CH3:1])=[CH:11][CH:10]=3)[CH:5]=[CH:6][C:7]2=[O:12])[CH2:32][CH2:31]1)[CH2:27][CH2:28][CH3:29]

Participants

11

Reactant 5

HCID 80061-Bromo-3-chloropropaneHCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 122374586-METHYLQUINOLIN-2(1H)-ONEHCID 132838674-Butylpiperidine

Product 1

HCID 17956184HCID 17956184, compoundYield 24%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A 4 mL vial was charged with 6-methyl-1H-quinolin-2-one (0.110 g, 0.71 mmol), dry DMF (2 mL) and NaH (60% in oil, 0.031 g, 0.78 mmol). The mixture was shaken under a N2 atmosphere for 1 h, and thereafter 1-bromo-3-chloropropane (70 μl, 0.71 mmol) was added. The reaction was shaken at rt for 20 h and then poured into diethyl ether (25 mL) and washed with water (15 mL). The ether phase was washed with water (15 mL) and brine (15 mL). The organic phase was dried over Na2SO4, and concentrated under reduced pressure. The residue was diluted with CH3CN (2 mL) and KI (0.160 g, 1.0 mmol), K2CO3 (0.140 g, 1.0 mmol) and 4-butylpiperidine (0.100 g, 0.71 mmol) was added. The mixture was shaken at 50° C. for 72 h and then poured onto The compound EtOAc (25 mL) and water (15 mL). The water phase was extracted (2×25 mL) and the combined organic phase was dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by flash CC (SiO2; EtOAc/MeOH 4:1) followed by prep RP-HPLC to give the title compound (0.058 g, 23%). 1H NMR (CD3OD) δ 7.78 (d, J=9.2 Hz, 1H), 7.52-7.40 (m, 3H), 6.60 (d, J=9.2 Hz, 1H), 4.3 (t, J=7.6 Hz, 2H), 2.92-2.2.85 (m, 2H), 2.50-2.39 (m, 2H), 2.39 (s, 3H), 1.99-1.84 (m, 4H), 1.69-1.61 (m, 2H), 1.35-1.11 (m, 9H), 0.88 (t, J=6.8 Hz); 13C NMR (CD3OD) δ 162.9, 140.1, 137.0, 132.5, 132.3, 128.8, 121.4, 120.2, 114.6, 55.8, 53.9, 40.6, 36.2, 35.7, 32.0, 28.9, 24.8, 22.8, 19.4, 13.3; HPLC-MS (ammonium acetate) [M+H]+=341.3.

Workup

  1. stirringThe reaction was shaken at rt for 20 h
  2. washwashed with water (15 mL)
  3. washThe ether phase was washed with water (15 mL) and brine (15 mL)
  4. dry with materialThe organic phase was dried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. additionwas added
  7. stirringThe mixture was shaken at 50° C. for 72 h
  8. extractionThe water phase was extracted (2×25 mL)
  9. dry with materialthe combined organic phase was dried over Na2SO4
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by flash CC (SiO2; EtOAc/MeOH 4:1)

Sources & evidence

ORD record
ord-9f81f3a756c344d88b5d3c5b5597bfc6
Source dataset
uspto-grants-2009_08
Patent number
US07576078B2

Reaction notes

Loading…