Cesium carbonate → 4-(3-Chloropropyl)-5,8-difluoro-4H-benzo[1,4]oxazin-3-one

HRID 1191503Notes

Reaction equation

HRID 1191503 reaction equation
[F:1][C:2]1[C:7]2[NH:8][C:9](=[O:12])[CH2:10][O:11][C:6]=2[C:5]([F:13])=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[Cl:20][CH2:21][CH2:22][CH2:23]I>>[Cl:20][CH2:21][CH2:22][CH2:23][N:8]1[C:7]2[C:2]([F:1])=[CH:3][CH:4]=[C:5]([F:13])[C:6]=2[O:11][CH2:10][C:9]1=[O:12]

Participants

4

Reactant 3

HCID 10796Cesium carbonateHCID 813631-Chloro-3-iodopropaneHCID 689120095,8-Difluoro-4H-benzo[1,4]oxazin-3-one

Product 1

HCID 689109514-(3-Chloropropyl)-5,8-difluoro-4H-benzo[1,4]oxazin-3-oneYield 17%

Procedure

5,8-Difluoro-4H-benzo[1,4]oxazin-3-one (1.86 g, 10 mmol), Cs2CO3 (4.91 g, 15 mmol), and 1-chloro-3-iodopropane (2.04 g, 10 mmol) were mixed according to GP2. Purified by column chromatography (SiO2; heptanes/EtOAc, gradient 0 to 50% EtOAc) to give the title compound (0.44 g, 17%). Rf=0.74 (heptanes/EtOAc 1:1); 1H NMR (CDCl3) δ 6.86-6.73 (m, 2H), 4.60 (s, 2H), 4.18-4.12 (m, 2H), 3.56 (t, J=6.4 Hz, 2H), 2.20-2.12 (m, 2H); 13C NMR (CDCl3) δ 164.7, 148.4 (dd, J=243.9 Hz, J=2.8 Hz), 147.5 (dd, J=243.7 Hz, J=3.0 Hz), 136.6 (dd, J=16.2 Hz, J=5.0 Hz), 119.8 (dd, J=11.2 Hz, J=2.7 Hz), 111.5 (dd, J=20.4 Hz, J=9.6 Hz), 110.4 (dd, J=24.8 Hz, J=7.9 Hz), 68.6, 42.4 (d, J=10.0 Hz), 42.1, 31.1 (d, J=3.5 Hz).

Workup

  1. customPurified by column chromatography (SiO2; heptanes/EtOAc, gradient 0 to 50% EtOAc)

Sources & evidence

ORD record
ord-00703458f8914e40b118be08d6fa24b2
Source dataset
uspto-grants-2014_03
Patent number
US08680115B2

Reaction notes

Loading…