Chlorotrimethylsilane → tert-Butyl 4-((trimethylsilyl)oxy)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 588475Notes

Reaction equation

[O:1]=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[CH3:15][Si:16](Cl)([CH3:18])[CH3:17].CCOC(C)=O.CCCCCC>CN(C=O)C>[CH3:15][Si:16]([CH3:18])([CH3:17])[O:1][C:2]1[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Tert-butyl 4-oxopiperidine-1-carboxylate, 1.1 (250 g, 1.256 mol) was taken in dry DMF (150 mL) under N2 atmosphere and added TEA (230 g, 2.27 mmol) at room temperature. The reaction mixture was cooled to 0° C., added trimethylsilyl chloride (178 g, 1.64 mol) drop wise for 30 minutes. After addition completed the reaction mixture heated at 80° C. for 16 h. The reaction was monitored by TLC (20% EtOAc/hexane), and allowed to cool the reaction mixture to room temperature, poured into ice water and extracted with EtOAc (3×200 mL). The combined organic layers were washed with water, brine solution, dried over Na2SO4 and evaporated under vacuum. The residue was purified by column chromatography on silica gel (5-10% EtOAc-Hexane) to afford tert-butyl 4-((trimethylsilyl)oxy)-5,6-dihydropyridine-1(2H)-carboxylate, 2.2 (300 g, 87.79%). 1HNMR (CDCl3, 400 MHz): δ 4.78 (s, 1H), 3.87-3.80 (m, 2H), 3.55 (t, 2H), 2.15-2.05 (m, 2H), 1.45 (s, 9H), 0.19 (s, 9H).

Workup

additionAfter addition
temperatureheated at 80° C. for 16 h
temperatureto cool the reaction mixture to room temperature
extractionextracted with EtOAc (3×200 mL)
washThe combined organic layers were washed with water, brine solution
dry with materialdried over Na2SO4
customevaporated under vacuum
customThe residue was purified by column chromatography on silica gel (5-10% EtOAc-Hexane)

Sources & evidence

ORD record: ord-8d31311748b5495ead375ef9a962652e
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09227969B2

Reaction notes

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