Imidazole → 6-{4-[(1R,2S)-2-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)cyclopropyl]piperidin-1-yl}pyridine-3-carbaldehyde

HRID 1474734Notes

Reaction equation

[OH:1][CH2:2][CH2:3][C@@H:4]1[CH2:6][C@@H:5]1[CH:7]1[CH2:12][CH2:11][N:10]([C:13]2[N:18]=[CH:17][C:16]([CH:19]=[O:20])=[CH:15][CH:14]=2)[CH2:9][CH2:8]1.N1C=CN=C1.[CH3:26][C:27]([Si:30](Cl)([CH3:32])[CH3:31])([CH3:29])[CH3:28]>CN(C=O)C.O>[Si:30]([O:1][CH2:2][CH2:3][C@@H:4]1[CH2:6][C@@H:5]1[CH:7]1[CH2:8][CH2:9][N:10]([C:13]2[N:18]=[CH:17][C:16]([CH:19]=[O:20])=[CH:15][CH:14]=2)[CH2:11][CH2:12]1)([C:27]([CH3:29])([CH3:28])[CH3:26])([CH3:32])[CH3:31]

Participants

Conditions

Temperature: 0 °C

Procedure

6-{4-[(1R,2S)-2-(2-hydroxyethyl)cyclopropyl]piperidin-1-yl}pyridine-3-carbaldehyde (1.5 g, 5.47 mmol) was dissolved in DMF (5.47 ml), and imidazole (0.558 g, 8.20 mmol) was added. The mixture was cooled to 0° C., TBDMS-Cl (0.989 g, 6.56 mmol) added and the mixture was allowed to warm to RT and stirred overnight. The mixture was diluted with 4:1 water:saturated sodium bicarbonate (100 ml), extracted with EtOAc (3×75 ml), the organic fractions combined, washed with brine, dried over Na2SO4, filtered and the volatiles removed in vac. The residue was purified by column chromatography on silica gel, Biotage 50 g, using a gradient eluant of 0-100% EtOAc/hexanes to afford the title compound. LC/MS (m/z): 389 (M+H)+.

Workup

temperatureto warm to RT
extractionsaturated sodium bicarbonate (100 ml), extracted with EtOAc (3×75 ml)
washwashed with brine
dry with materialdried over Na2SO4
filtrationfiltered
customthe volatiles removed in vac
customThe residue was purified by column chromatography on silica gel, Biotage 50 g

Sources & evidence

ORD record: ord-a02961b24f7c4ddf981d4b6d662fac82
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09018224B2

Reaction notes

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