Potassium Carbonate → 4-[3-(4-Cyclopropylmethoxypiperidin-1-yl)propyl]-6,8-difluoro-4H-benzo[1,4]oxazin-3-one

HRID 1191517Notes

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[CH:22]=[C:23]([F:27])[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[CH:22]=[C:23]([F:27])[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 689081734-(3-Chloropropyl)-6,8-difluoro-4H-benzo[1,4]oxazin-3-one

Product 1

HCID 689129194-[3-(4-Cyclopropylmethoxypiperidin-1-yl)propyl]-6,8-difluoro-4H-benzo[1,4]oxazin-3-oneYield 50.4%

Procedure

4-Cyclopropylmethoxypiperidine (0.076 g, 0.49 mmol), 4-(3-chloropropyl)-6,8-difluoro-4H-benzo[1,4]oxazin-3-one (0.143 g, 0.55 mmol), K2CO3 (0.136 g, 0.98 mmol) and KI (0.147 g, 0.98 mmol) were mixed according to GP3. Purified by prep TLC (SiO2; heptanes/EtOAc 1:1) to give the title compound (0.094 g, 50%). 1H NMR (CDCl3) δ 6.83-6.78 (m, 1H), 6.60-6.54 (m, 1H), 4.60 (s, 1H), 3.92 (t, J=6.8 Hz, 2H), 3.36-3.24 (m, 3H), 2.77-2.68 (m, 2H), 2.34 (t, J=6.8 Hz, 2H), 2.09 (t, J=9.6 Hz, 2H), 1.93-1.76 (m, 4H), 1.66-1.56 (m, 2H), 1.08-0.97 (m, 1H), 0.53-0.48 (m, 2H), 0.19-0.15 (m, 2H); 13C NMR (CDCl3) δ 163.9, 157.4 (dd, J=241.4 Hz, J=12.7 Hz), 151.4 (dd, J=247.6 Hz, J=14.3 Hz), 131.4 (dd, J=12.5 Hz, J=4.7 Hz), 130.2 (dd, J=14.6 Hz, J=3.9 Hz), 99.3 (dd, J=26.9 Hz, J=22.3 Hz), 98.6 (dd, J=28.4 Hz, J=3.5 Hz), 74.8, 72.8, 67.8, 55.1, 51.5, 40.3, 31.5, 24.8, 11.1, 3.2.

Workup

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

Sources & evidence

ORD record: ord-ad1cb2ea57694b11a1110dab28490e68
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08680115B2

Reaction notes

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