Potassium Carbonate → 4-[3-(4-Cyclopropylmethoxypiperidin-1-yl)propyl]-5,8-difluoro-4H-benzo[1,4]oxazin-3-one

HRID 1191518Notes

Reaction equation

[CH:1]1([CH2:4][O:5][CH:6]2[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]2)[CH2:3][CH2:2]1.Cl[CH2:13][CH2:14][CH2:15][N:16]1[C:21]2[C:22]([F:27])=[CH:23][CH:24]=[C:25]([F:26])[C:20]=2[O:19][CH2:18][C:17]1=[O:28].C([O-])([O-])=O.[K+].[K+]>>[CH:1]1([CH2:4][O:5][CH:6]2[CH2:11][CH2:10][N:9]([CH2:13][CH2:14][CH2:15][N:16]3[C:21]4[C:22]([F:27])=[CH:23][CH:24]=[C:25]([F:26])[C:20]=4[O:19][CH2:18][C:17]3=[O:28])[CH2:8][CH2:7]2)[CH2:2][CH2:3]1

Participants

Reactant 3

HCID 11430Potassium Carbonate

HCID 171780104-(Cyclopropylmethoxy)piperidine

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

Product 1

HCID 689147554-[3-(4-Cyclopropylmethoxypiperidin-1-yl)propyl]-5,8-difluoro-4H-benzo[1,4]oxazin-3-oneYield 37.3%

Procedure

4-Cyclopropylmethoxypiperidine (0.085 g, 0.55 mmol), 4-(3-chloropropyl)-5,8-difluoro-4H-benzo[1,4]oxazin-3-one (0.146 g, 0.56 mmol), K2CO3 (0.152 g, 1.1 mmol), and KI (0.164 g, 1.1 mmol) were mixed according to GP3. Purified by prep TLC (SiO2; Heptanes/EtOAc 1:1) to give the title compound (0.078 g, 37%). 1H NMR (CDCl3) δ 6.82-6.69 (m, 2H), 4.57 (s, 2H), 4.07-4.03 (m, 2H), 3.31-3.22 (m, 3H), 2.72-2.64 (m, 2H), 2.32 (t, J=7.2 Hz, 2H), 2.02 (t, J=10.4 Hz, 2H), 1.88-1.76 (m, 4H), 1.59-1.48 (m, 2H), 1.07-0.95 (m, 2H), 0.53-0.47 (m, 2H), 0.19-0.14 (m, 2H); 13C NMR (CDCl3) δ 164.6, 148.3 (dd, J=243.3 Hz, J=2.7 Hz), 147.7 (dd, J=243.9, J=2.8 Hz), 136.6 (dd, J=11.2 Hz, J=4.9 Hz), 120.0 (d, J=11.1 Hz), 111.2 (dd, J=20.4 Hz, J=9.6 Hz), 110.3 (dd, J=24.8 Hz, J=7.7 Hz), 75.0, 72.6, 68.6, 55.6, 51.5, 42.7 (d, J=10.8 Hz), 31.5, 25.7 (d, J=2.7 Hz), 11.1, 3.2.

Workup

customPurified by prep TLC (SiO2; Heptanes/EtOAc 1:1)

Sources & evidence

ORD record: ord-3ec67f22e450461099eae12ffb2efcd9
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08680115B2

Reaction notes

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