Potassium Carbonate → tert-Butyl (trans-4-((3-nitropyridin-2-yl)amino)cyclohexyl)carbamate
Reaction equation
[C:1]([NH:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([NH2:15])[CH2:11][CH2:10]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(=O)([O-])[O-].[K+].[K+].F[C:23]1[C:28]([N+:29]([O-:31])=[O:30])=[CH:27][CH:26]=[CH:25][N:24]=1>C1(C)C=CC=CC=1>[CH3:5][C:4]([O:3][C:1]([NH:8][CH:9]1[CH2:10][CH2:11][CH:12]([NH:15][C:23]2[N:24]=[CH:25][CH:26]=[CH:27][C:28]=2[N+:29]([O-:31])=[O:30])[CH2:13][CH2:14]1)=[O:2])([CH3:7])[CH3:6]Participants
Conditions
- Temperature
- 120 °C
Procedure
To a flask charged with toluene (37.3 mL) were added trans-N-boc-1,4-cyclohexanediamine (2.00 g, 9.33 mmol), potassium carbonate (1.290 g, 9.33 mmol) and 2-fluoro-3-nitropyridine (commercially available from Matrix Scientific, Columbia, S.C.) (1.326 mL, 9.33 mmol). The resulting bright yellow solution was heated overnight at 120° C. leading to conversion to the desired product as the primary species along with a more polar impurity according to LC-MS. The mixture was diluted with water, transferred to a separatory funnel and extracted with EtOAc (2×). The combined organic layers were dried with Na2SO4, filtered, and dried under reduced pressure providing a bright yellow solid which was triturated with DCM providing tert-butyl ((1r,4r)-4-((3-nitropyridin-2-yl)amino)cyclohexyl)carbamate (1.51 g, 4.49 mmol, 48.1% yield) as a bright yellow solid. 1H NMR (400 MHz, DMSO-d6) δ=8.49 (dd, J=1.8, 4.5 Hz, 1H), 8.41 (dd, J=1.8, 8.4 Hz, 1H), 8.06 (d, J=7.7 Hz, 1H), 6.79-6.69 (m, 2H), 4.13-4.00 (m, J=3.9, 7.4, 7.4, 11.3 Hz, 1H), 3.29-3.20 (m, 1H), 2.01-1.92 (m, 2H), 1.82 (d, J=10.6 Hz, 2H), 1.55-1.41 (m, 2H), 1.38 (s, 9H), 1.35-1.21 (m, 2H). m/z (ESI) 281.2 (M+H)+.
Sources & evidence
- ORD record
- ord-35591a869dd24cd9a88a67450f1ee648
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09340549B2
Reaction notes
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