1-Bromo-3-chloropropane → HCID 17956115, compound

HRID 2103271Notes

Reaction equation

HRID 2103271 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])[CH2:6][CH2:5]2.[H-].[Na+].Br[CH2:16][CH2:17][CH2:18]Cl.[CH2:20]([CH:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1)[CH2:21][CH2:22][CH3:23].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH2:20]([CH:24]1[CH2:29][CH2:28][N:27]([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)[CH2:5][CH2:6][C:7]2=[O:12])[CH2:26][CH2:25]1)[CH2:21][CH2:22][CH3:23]

Participants

7

Reactant 5

HCID 80061-Bromo-3-chloropropaneHCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 112408256-chloro-3,4-dihydro-1H-quinolin-2-oneHCID 132838674-Butylpiperidine

Product 1

HCID 17956115HCID 17956115, compoundYield 235.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A reaction flask was charged with 6-chloro-3,4-dihydro-1H-quinolin-2-one (107LH30) (0.100 g, 0.55 mmol) in dry DMF (2 mL) under Argon. NaH (60% in oil, 0.024 g, 0.60 mmol) was added and the mixture was stirred at rt for 0.5 h. Then 1-bromo-3-chloropropane (0.087 g, 0.55 mmol) was added followed by stirring at 30° 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 crude material was dissolved in MeCN (3 mL) followed by addition of 4-butylpiperidine (0.078 g, 0.055 mmol), KI (0.166 g, 1.00 mmol), and K2CO3 (0.138 g, 1.00 mmol) and shaken at 50° for 2 days. 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 prep RP-HPLC to give the title compound (107LH36) (0.047 g, 24%). 1H NMR (CD3OD) δ 7.25-7.13 (m, 3H), 3.96 (t, J=7.2 Hz, CH2), 2.95-2.86 (m, 4H), 2.61-2.57 (m, 2H), 2.45-2.41 (m, 2H), 2.04-1.98 (m, 2H), 1.87-1.79 (m, 2H), 1.28-1.18 (m, 9H), 0.90 (t, J=7.0 Hz, CH3); 13C NMR (CD3OD) δ 172.3, 139.2, 130.2, 129.3, 128.9, 128.4, 117.8, 56.8, 54.9, 41.4, 37.2, 36.6, 32.9, 32.4, 30.0, 26.0, 25.3, 23.9, 14.4; HPLC-MS (ammonium acetate) [M+H+]=363.28.

Workup

  1. stirringby stirring at 30° for 20 h
  2. customThe reaction mixture was quenched with water
  3. extractionthe product extracted into EtOAc
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe crude material was dissolved in MeCN (3 mL)
  8. stirringshaken at 50° for 2 days
  9. customThe reaction mixture was quenched with water
  10. extractionthe product extracted into EtOAc
  11. dry with materialThe combined organic layers were dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe product was purified by prep RP-HPLC

Sources & evidence

ORD record
ord-581b0b59d43b4ecd9c9147924283a5cf
Source dataset
uspto-grants-2009_08
Patent number
US07576100B2

Reaction notes

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