Hydrochloric Acid → (R)-ethyl 6-bromo-1-(1-(tert-butoxycarbonyl)piperidin-3-yl)-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate

HRID 1047156Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[N:4][C:5](F)=[C:6]([CH:19]=1)[C:7]([C:9](=[CH:15][N:16]([CH3:18])C)[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[O:8].N[C@@H:22]1[CH2:27]C[CH2:25][N:24]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:23]1.C(=O)([O-])[O-].[K+].[K+].Cl>C1COCC1.CN(C=O)C>[Br:1][C:2]1[CH:19]=[C:6]2[C:5](=[N:4][CH:3]=1)[N:16]([C@@H:18]1[CH2:27][CH2:22][CH2:23][N:24]([C:28]([O:30][C:31]([CH3:32])([CH3:34])[CH3:33])=[O:29])[CH2:25]1)[CH:15]=[C:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:7]2=[O:8]

Participants

Conditions

Temperature: 60 °C

Procedure

Ethyl 2-(5-bromo-2-fluoronicotinoyl)-3-(dimethylamino)acrylate (Intermediate 3, 2.0 g, 5.79 mmol), (R)-tert-butyl 3-aminopiperidine-1-carboxylate (1.160 g, 5.79 mmol, CNH technologies), and potassium carbonate (2.042 g, 7.38 mmol, Aldrich) were combined in THF (10.0 mL). The reaction was heated at 60° C. for 2 hrs. After 2 h, DMF (5.0 mL) was added. The reaction was heated at 90° C. for 14 h. The reaction mixture was cooled to 0° C. and 1N HCl was slowly added until pH was around 4. The resulting precipitate was filtered, washed with water and dried overnight to yield a light yellow solid (2.10 g, 75%).

Workup

temperatureThe reaction was heated at 90° C. for 14 h
temperatureThe reaction mixture was cooled to 0° C.
filtrationThe resulting precipitate was filtered
washwashed with water
customdried overnight

Sources & evidence

ORD record: ord-5fe6874c42b24d9ca8ac78ba953e3fc3
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08569484B2

Reaction notes

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