Cesium carbonate → HCID 10286748, compound

HRID 2103240Notes

Reaction equation

HRID 2103240 reaction equation
Cl[CH2:2][C:3]([CH2:5]Cl)=[CH2:4].[O:7]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[NH:10][C:9](=[O:17])[CH2:8]1.C([O-])([O-])=O.[Cs+].[Cs+].[CH2:24]([CH:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)[CH2:25][CH2:26][CH3:27]>CCOCC.CN(C=O)C>[CH2:24]([CH:28]1[CH2:33][CH2:32][N:31]([CH2:4][C:3](=[CH2:2])[CH2:5][N:10]2[C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[O:7][CH2:8][C:9]2=[O:17])[CH2:30][CH2:29]1)[CH2:25][CH2:26][CH3:27]

Participants

7

Reactant 4

HCID 10796Cesium carbonate2×HCID 158593-Chloro-2-chloromethyl-1-propeneHCID 727572H-1,4-benzoxazin-3(4H)-oneHCID 132838674-Butylpiperidine

Product 1

HCID 10286748HCID 10286748, compoundYield 59.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
65 °C

Procedure

3-Chloro-2-chloromethyl-1-propene (0.20 g, 1.5 mmol), 4H-benzo[1,4]oxazin-3-one (0.15 g, 1.0 mmol) and Cs2CO3 (0.65 g, 2.0 mmol) were mixed with 1 mL DMF and were shaken at 65° C. for 5 h. The mixture was diluted with ether (20 mL) and washed with water (20 mL) and the water phase was extracted with ether (20 mL). The combined organic phase was washed with brine (10 mL), dried over Na2SO4, filtered concentrated under reduced pressure and the residue was purified by flash CC (SiO2; heptane/EtOAc 70:30). This product (0.080 g, 0.34 mmol) was dissolved in DMF (1 mL), thereafter 4-butylpiperidine (0.053 g, 0.37 mmol) and Cs2CO3 (0.23 g, 0.71 mmol) were added and the mixture was shaken at 65° C. for 24 h. The mixture was then poured into ether (25 mL) washed with water (10 mL) and the water phase was extracted with ether (20 mL). The combined organic phase was washed with brine (10 mL), dried over Na2SO4, filtered, concentrated under reduced pressure and the residue was purified by cation exchange CC, followed by flash CC (SiO2; EtOAc/MeOH/NH4OH (25% NH3 in water) 97.5:2:0.5), to yield the title compound (0.075 g, 21%). 1H NMR (CDCl3) δ 7.05-2.92 (m, 4H), 5.01 (brs, 1H), 4.82 (brs, 1H), 4.64 (brs 2H), 4.57 (brs, 2H), 2.94 (brs, 2H), 2.86 (brd, J=10.4 Hz, 2H), 1.93-1.82 (m, 2H), 1.71-1.62 (m, 2H), 1.34-1.15 (m, 9H), 0.89 (t, J=6.2 Hz, 3H); 13C NMR (CDCl3) δ 1.64.5, 145.4, 129.2, 123.9, 122.8, 116.9, 113.2, 67.9, 63.2, 54.4, 44.8, 36.6, 36.0, 32.8, 29.3, 23.1, 14.3; HPLC-MS (ammonium acetate) [M+H]+=343.3.

Workup

  1. washwashed with water (20 mL)
  2. extractionthe water phase was extracted with ether (20 mL)
  3. washThe combined organic phase was washed with brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customthe residue was purified by flash CC (SiO2; heptane/EtOAc 70:30)
  8. stirringthe mixture was shaken at 65° C. for 24 h
  9. washwashed with water (10 mL)
  10. extractionthe water phase was extracted with ether (20 mL)
  11. washThe combined organic phase was washed with brine (10 mL)
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customthe residue was purified by cation exchange CC

Sources & evidence

ORD record
ord-39f8441b638b40ca9e56c5823fce3a78
Source dataset
uspto-grants-2009_08
Patent number
US07576100B2

Reaction notes

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