Cesium carbonate → 4-(3-Chloropropyl)-6,8-difluoro-4H-benzo[1,4]oxazin-3-one

HRID 1191505Notes

Reaction equation

HRID 1191505 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([F:13])[C:5]2[O:10][CH2:9][C:8](=[O:11])[NH:7][C:6]=2[CH:12]=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:7]1[C:6]2[CH:12]=[C:2]([F:1])[CH:3]=[C:4]([F:13])[C:5]=2[O:10][CH2:9][C:8]1=[O:11]

Participants

4

Reactant 3

HCID 10796Cesium carbonateHCID 813631-Chloro-3-iodopropaneHCID 552528146,8-difluoro-3,4-dihydro-2H-1,4-benzoxazin-3-one

Product 1

HCID 689081734-(3-Chloropropyl)-6,8-difluoro-4H-benzo[1,4]oxazin-3-oneYield 39.1%

Procedure

6,8-Difluoro-4H-benzo[1,4]oxazin-3-one (0.80 g, 4.3 mmol), Cs2CO3 (2.12 g, 6.5 mmol), and 1-chloro-3-iodopropane (0.98 g, 4.8 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, 39%). Rf=0.65 (heptanes/EtOAc 1:1); 1H NMR (CDCl3) δ 6.66-6.59 (m, 2H), 4.64 (s, 2H), 4.09-4.03 (m, 2H), 3.62 (t, J=6.0 Hz, 2H), 2.23-2.10 (m, 2H); 13C NMR (CDCl3) δ 164.2, 157.5 (dd, J=242.5 Hz, J=12.7 Hz), 151.7 (dd, J=248.5 Hz, J=14.4 Hz), 131.0 (dd, J=12.1 Hz, J=4.8 Hz), 130.4 (dd, J=15.0 Hz, J=3.2 Hz), 99.7 (dd, J=26.9 Hz, J=22.4 Hz), 98.2 (dd, J=28.4 Hz, J=3.4 Hz), 67.8, 42.2, 39.7, 30.0.

Workup

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

Sources & evidence

ORD record
ord-9244dbdac0524426af5049ae6220ff26
Source dataset
uspto-grants-2014_03
Patent number
US08680115B2

Reaction notes

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