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

HRID 877666Notes

Reaction equation

HRID 877666 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.C(N(CC)CC)C.[CH3:22][Si:23](Cl)([CH3:25])[CH3:24]>CN(C=O)C.CCCCCC>[CH3:22][Si:23]([CH3:25])([CH3:24])[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

6

Reactant 3

HCID 6397ChlorotrimethylsilaneHCID 8471TriethylamineHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 10778540tert-Butyl 4-((trimethylsilyl)oxy)-5,6-dihydropyridine-1(2H)-carboxylateYield 88.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8058HexaneSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of tert-butyl 4-oxopiperidine-1-carboxylate (1.0 g, 5 mmol) in dry DMF (5 mL) under argon was added triethylamine (1.67 mL, 12 mmol) followed by TMSCl (0.95 mL, 7.5 mmol), and the reaction mixture was stirred at 80° C. for 16 h under argon. The reaction mixture was diluted with hexane (10 mL) and washed with cold saturated sodium bicarbonate (3×10 mL). The organic layer was dried over anhyd. Na2SO4 and concentrated under vacuum. The crude product obtained was purified by flash chromatography to give the title compound as a colorless oil (1.2 g, 88%). LCMS (Condition D): m/z 272 +ve with retention time=2.18 min. 1H-NMR (400 MHz, CDCl3): δ ppm: 4.80 (s, 1H), 3.88 (bs, 1H), 3.52-3.55 (t, J=6 Hz, 2H), 2.11 (bs, 2H), 1.47 (s, 9H), 0.20 (s, 9H).

Workup

  1. washwashed with cold saturated sodium bicarbonate (3×10 mL)
  2. customThe organic layer was dried over anhyd
  3. concentrationNa2SO4 and concentrated under vacuum
  4. customThe crude product obtained
  5. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-c43f0bf8693f47238a60e20c986bcf50
Source dataset
uspto-grants-2015_03
Patent number
US08987268B2

Reaction notes

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