Ethyl Acetate → tert-Butyl [1-(5-methylpyridin-2-yl)piperidin-4-yl]carbamate

HRID 2239565Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N:3]=1.[NH:9]1[CH2:14][CH2:13][CH:12]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:11][CH2:10]1.C1CCN2C(=NCCC2)CC1.CCOC(C)=O>CS(C)=O>[CH3:8][C:5]1[CH:6]=[CH:7][C:2]([N:9]2[CH2:10][CH2:11][CH:12]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:20])([CH3:19])[CH3:21])[CH2:13][CH2:14]2)=[N:3][CH:4]=1

Participants

Conditions

Temperature: 110 °C

Procedure

A solution of 2-bromo-5-methylpyridine (1.00 g, 5.8 mmol), tert-butyl piperidine-4-ylcarbamate (1.28 g, 6.39 mmol) and TEA (1.21 ml, 8.72 mmol) in DMSO (5 ml) was heated at 110° C., After 17 h the reaction mixture was heated at 130° C. for 4 h before more TEA (0.40 ml, 2.91 mmol) was added. After 2.5 h, DBU (1.73 ml, 11.63 mmol) was added and the reaction mixture heated at 110° C. for 17 h. The reaction mixture was then allowed to cool to rt and EtOAc was added. The reaction mixture was washed with brine and evaporated to dryness. The residue was purified using the Biotage SPI eluting with 25% EtOAc in pet. ether 40-60° C. to give the title compound (0.233 g, 14%) as a solid. 1H NMR (500 MHz, CDCl3): 8.02 (d, 1H), 7.31 (dd, 1H), 6.62 (d, 1H), 4.48 (bs, 1H), 4.16-4.10 (m, 2H), 3.68 (bs, 1H), 2.95 (dt, 2H), 2.20 (s, 3H), 2.08-2.00 (m, 2H), 1.48-1.40 (m, 9H). 13C NMR (CDCl3): 158.1, 155.4, 147.9, 138.6, 122.3, 107.5, 79.5, 48.4, 45.1, 32.3, 28.7, 17.5. Mass Spectrum: M+H 292.

Workup

additionwas added
temperatureto cool to rt
washThe reaction mixture was washed with brine
customevaporated to dryness
customThe residue was purified
customwith 25% EtOAc in pet. ether 40-60° C.

Sources & evidence

ORD record: ord-6d21fc2c6cf74fa3946944ed00fe8ad0
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07723333B2

Reaction notes

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