1-Bromo-3-chloropropane → HCID 17956069, compound

HRID 2103294Notes

Reaction equation

HRID 2103294 reaction equation
[Cl: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]>CCOCC.CC#N.CCOC(C)=O.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]([Cl: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

10

Reactant 5

HCID 80061-Bromo-3-chloropropaneHCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 3266466-Chloro-2-hydroxyquinolineHCID 132838674-Butylpiperidine

Product 1

HCID 17956069HCID 17956069, compoundYield 49.4%

Reagents, catalysts & solvents 4

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A 4 mL vial was charged with 6-chloro-1H-quinolin-2-one (107LH35) (0.085 g, 0.47 mmol), dry DMF (3 mL) and NaH (60% in oil, 0.023 g, 0.56 mmol) and the mixture was stirred at rt for 45 min under a N2 atmosphere. Thereafter, 1-bromo-3-chloropropane (18 μl, 0.18 mmol) was added and the mixture was shaken at rt overnight, the reaction diluted with ether (25 mL) and washed with water (15 mL). The ether phase was washed with brine (15 mL), dried over Na2SO4, concentrated under reduced pressure. The oily residue was diluted with dry CH3CN (2 mL) and KI (0.170 g, 1.0 mmol), K2CO3 (0.140 g, 1.0 mmol) and 4-butylpiperidine (0.071 g, 0.50 mmol) were added. The mixture was shaken at 50° C. for 24 h and then diluted with EtOAc (25 mL) and washed with water (15 mL). The water phase was extracted (2×25 mL) and the combined organic phases were dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by prep RP-HPLC to give the title compound (32 mg, 89 μmol, 19%). 1H NMR (CD3OD) δ 7.80 (d, J=9.2 Hz, 1H), 7.66 (brs, 1H), 7.60-7.51 (m, 2H), 6.65 (d, J=9.6 Hz, 1H), 5.30 (t, J=7.6 Hz, 2H), 3.09-2.95 (m, 2H), 2.68-2.57 (m, 2H), 2.24-2.06 (m 2H), 2.00-1.90 (m, 2H), 1.75-1.64 (m, 2H), 1.32-1.12 (m, 9H), 0.84 (t, 6.4 Hz, 3H); 13C NMR (CD3OD) δ 162.6, 139.2, 137.4, 130.8, 128.0, 127.8, 122.4, 121.5, 116.3, 55.0, 53.3, 40.3, 35.7, 34.8, 31.0, 28.6, 23.9, 22.5, 13.0; HPLC-MS (ammonium acetate) [M+H]+=361.3.

Workup

  1. stirringthe mixture was shaken at rt overnight
  2. washwashed with water (15 mL)
  3. washThe ether phase was washed with brine (15 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. additionwere added
  7. stirringThe mixture was shaken at 50° C. for 24 h
  8. washwashed with water (15 mL)
  9. extractionThe water phase was extracted (2×25 mL)
  10. dry with materialthe combined organic phases were dried over Na2SO4
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by prep RP-HPLC

Sources & evidence

ORD record
ord-817a89340d9740ee84ce919011dcc12d
Source dataset
uspto-grants-2009_08
Patent number
US07576100B2

Reaction notes

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