Potassium Carbonate → 4-[3-(4-Cyclopropylmethoxypiperidin-1-yl)propyl]-5,6-difluoro-4H-benzo[1,4]oxazin-3-one

HRID 1986848Notes

Reaction equation

HRID 1986848 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])=[C:23]([F:26])[CH:24]=[CH:25][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])=[C:23]([F:26])[CH:24]=[CH:25][C:20]=4[O:19][CH2:18][C:17]3=[O:28])[CH2:8][CH2:7]2)[CH2:2][CH2:3]1

Participants

4

Reactant 3

HCID 11430Potassium CarbonateHCID 171780104-(Cyclopropylmethoxy)piperidineHCID 689103024-(3-chloropropyl)-5,6-difluoro-4H-benzo[1,4]oxazin-3-one

Product 1

HCID 689110504-[3-(4-Cyclopropylmethoxypiperidin-1-yl)propyl]-5,6-difluoro-4H-benzo[1,4]oxazin-3-oneYield 54%

Procedure

4-Cyclopropylmethoxypiperidine (0.037 g, 0.24 mmol), 4-(3-chloropropyl)-5,6-difluoro-4H-benzo[1,4]oxazin-3-one (0.065 g, 0.25 mmol), K2CO3 (0.06 g, 0.48 mmol), and KI (0.072 g, 0.48 mmol) were mixed according to GP3. Purified by prep TLC (SiO2; heptanes/EtOAc 1:1) to give the title compound (0.049 g, 54%). Rf=0.21 (heptanes/EtOAc 1:1); 1H NMR (CDCl3) d 6.84-6.70 (m, 2H), 4.48 (s, 2H), 4.48 (s, 2H), 4.08-4.02 (m, 2H), 3.34-3.26 (m, 1H), 3.24 (d, J=6.8 Hz, 2H), 2.75-2.68 (m 2H), 2.38 (t, J=7.2 Hz, 2H), 2.18-2.06 (m, 2H), 1.92-1.81 (m, 4H), 1.63-1.52 (m, 2H), 1.06-0.96 (m, 2H), 0.52-0.47 (m, 2H), 0.18-0.14 (m, 2H); 13C NMR (CDCl3) d 165.0, 147.5 (dd, J=242.3 Hz, J=13.2 Hz), 143.9, 140.7 (dd, J=250.2 Hz, J=17.3 Hz), 119.9, 111.7 (dd, J=7.3 Hz, J=3.5 Hz), 110.9 (d, J=18.9 Hz), 74.5, 72.7, 68.5, 55.5, 51.2, 42.7 (d, J=10.4 Hz), 31.1, 25.5, (d, J=2.6 Hz), 11.1, 3.2.

Workup

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

Sources & evidence

ORD record
ord-d3677241e7ee408288c4ed3020105899
Source dataset
uspto-grants-2009_06
Patent number
US07550459B2

Reaction notes

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