Potassium Carbonate → 4-[3-(4-Cyclopropylmethoxypiperidin-1-yl)propyl]-7-fluoro-4H-benzo[1,4]oxazin-3-one

HRID 1191515Notes

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]=[CH:23][C:24]([F:26])=[CH:25][C:20]=2[O:19][CH2:18][C:17]1=[O:27].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]=[CH:23][C:24]([F:26])=[CH:25][C:20]=4[O:19][CH2:18][C:17]3=[O:27])[CH2:8][CH2:7]2)[CH2:2][CH2:3]1

Participants

Reactant 3

HCID 11430Potassium Carbonate

HCID 171780104-(Cyclopropylmethoxy)piperidine

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

Product 1

HCID 116890894-[3-(4-Cyclopropylmethoxypiperidin-1-yl)propyl]-7-fluoro-4H-benzo[1,4]oxazin-3-oneYield 50.1%

Procedure

4-Cyclopropylmethoxypiperidine (0.042 g, 0.27 mmol), 4-(3-chloropropyl)-7-fluoro-4H-benzo[1,4]oxazin-3-one (0.08 g, 0.32 mmol), K2CO3 (0.075 g, 0.54 mmol) and KI (0.081 g, 0.54 mmol) were mixed according to GP3. Purified by prep TLC (SiO2; heptanes/EtOAc 1:1) to give the title compound (0.049 g, 42%). Rf=0.47 (CH2Cl2/MeOH 10:1); 1H NMR (CDCl3) δ 7.09-7.04 (m, 1H), 6.75-6.69 (m, 2H), 4.57 (s, 2H), 3.95 (t, J=7.2 Hz), 3.34-3.25 (m, 3H), 2.77-2.70 (m, 2H), 2.36 (t, J=6.8 Hz, 2H), 2.11-2.02 (m, 2H), 1.93-1.76 (m, 4H), 1.64-1.54 (m, 2H), 1.09-0.98 (m, 1H), 0.55-0.49 (m, 2H), 0.21-0.16 (m, 2H); 13C NMR (CDCl3) δ 163.6, 158.9 (d, J=243.7 Hz), 146.3 (d, J=11.6 Hz), 125.2 (d, J=3.1 Hz), 115.8 (t, J=11.2 Hz), 109.2 (d, J=22.3 Hz), 105.2 (dd, J=25.7 Hz, J=3.8 Hz), 75.0, 72.8, 67.8 (t, J=8.1 Hz), 55.4, 51.6 (J=9.2 Hz), 39.9 (t, J=12.3 Hz), 31.7, 24.9, 11.1, 3.2.

Workup

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

Sources & evidence

ORD record: ord-34346ba0369048919701534db06258b6
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08680115B2

Reaction notes

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