Cesium carbonate → 4-(3-Chloropropyl)-7-fluoro-4H-benzo[1,4]oxazin-3-one

HRID 1986840Notes

Reaction equation

HRID 1986840 reaction equation
F[C:2]1[C:3]([F:13])=[CH:4][C:5]2[O:10][CH2:9][C:8](=[O:11])[NH:7][C:6]=2[CH:12]=1.[Cl:14][CH2:15][CH2:16][CH2:17]I.C([O-])([O-])=O.[Cs+].[Cs+]>CC#N>[Cl:14][CH2:15][CH2:16][CH2:17][N:7]1[C:6]2[CH:12]=[CH:2][C:3]([F:13])=[CH:4][C:5]=2[O:10][CH2:9][C:8]1=[O:11]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 813631-Chloro-3-iodopropaneHCID 469303446,7-Difluoro-4H-benzo[1,4]oxazin-3-one

Product 1

HCID 688939964-(3-Chloropropyl)-7-fluoro-4H-benzo[1,4]oxazin-3-oneYield 95.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A reaction flask was charged with 6,7-difluoro-4H-benzo[1.4]oxazin-3-one (1.5 g, 8.1 mmol), 1-chloro-3-iodopropane (1.44 g, 8.1 mmol), and Cs2CO3 (4.0 g, 12.2 mmol) in MeCN (10 mL) and stirred at rt for 40 h. The reaction mixture was concentrated, water added, and the product extracted into EtOAc. The combined organic phases were dried over Na2SO4, filtered, and concentrated. The product was purified by flash column chromatography (SiO2; n-heptane/EtOAc 2:1) to give the title compound (1.88 g, 89%). 1H NMR (CDCl3) d 6.99 (dd, J=8.0 Hz, J=5.6 Hz, 1H), 6.79-6.72 (m, 2H), 4.59 (s, 2H), 4.08 (t, J=7.2 Hz, 2H), 3.62 (t, J=6.0 Hz, 2H) 2.18-2.10 (m, 2H); 13C NMR (CDCl3) d 163.9, 159.1 (d, J=244.1 Hz), 146.4 (d, J=11.9 Hz), 124.9 (d, J=3.0 Hz), 115.4 (d, J=9.6 Hz), 109.5 (d, J=22.7 Hz), 105.4 (d, J=26.2 Hz), 67.7, 42.4, 39.2, 30.1.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionwater added
  3. extractionthe product extracted into EtOAc
  4. dry with materialThe combined organic phases were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe product was purified by flash column chromatography (SiO2; n-heptane/EtOAc 2:1)

Sources & evidence

ORD record
ord-676862c62b96469cafbee869ea107615
Source dataset
uspto-grants-2009_06
Patent number
US07550459B2

Reaction notes

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