Triethylamine → 1-(2-Methoxy-4-nitro-phenyl)-4-triisopropylsilanyloxy-piperidine

HRID 601503Notes

Reaction equation

HRID 601503 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[CH:5][C:4]=1[N:12]1[CH2:17][CH2:16][CH:15]([OH:18])[CH2:14][CH2:13]1.[CH:19]([Si:22](OS(C(F)(F)F)(=O)=O)([CH:26]([CH3:28])[CH3:27])[CH:23]([CH3:25])[CH3:24])([CH3:21])[CH3:20].CCN(CC)CC>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[CH:5][C:4]=1[N:12]1[CH2:17][CH2:16][CH:15]([O:18][Si:22]([CH:26]([CH3:28])[CH3:27])([CH:23]([CH3:25])[CH3:24])[CH:19]([CH3:21])[CH3:20])[CH2:14][CH2:13]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2724529Triisopropylsilyl trifluoromethanesulfonateHCID 574214671-(2-Methoxy-4-nitro-phenyl)-piperidin-4-ol

Product 1

HCID 575017001-(2-Methoxy-4-nitro-phenyl)-4-triisopropylsilanyloxy-piperidineYield 80.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Dissolve 1-(2-methoxy-4-nitro-phenyl)-piperidin-4-ol (1.19 g, 4.72 mmol) in DMF (25 mL), followed by addition of triisopropylsilyl-trifluoromethanesulfonate (1.50 mL, 5.56 mmol) and Et3N (0.80 mL, 5.87 mmol). Stir the solution at room temperature for 2 h, then add water (50 mL) and extract with EtOAc (2×50 mL). Combine the organic solutions and wash with water (2×30 mL) and brine (30 mL), then dry, filter, and concentrate. Purify the crude material by flash chromatography, using a linear gradient of 100% hexanes to 20% EtOAc/hexanes, to give the title compound as a yellow solid (1.55 g, 80%). MS (ES+) 409.3 (M+1)+. 1H NMR (400 MHz, CDCl3) δ: 7.84 (dd, 1H, J=8.8, 2.6 Hz), 7.68 (d, 1H, J=2.6 Hz), 6.89 (d, 1H, J=8.8 Hz), 4.07-4.01 (m, 1H), 3.93 (s, 3H), 3.45-3.38 (m, 2H), 3.13-3.06 (m, 2H), 1.99-1.91 (m, 2H), 1.81-1.73 (m, 2H), 1.07-1.06 (m, 21H).

Workup

  1. extractionadd water (50 mL) and extract with EtOAc (2×50 mL)
  2. washCombine the organic solutions and wash with water (2×30 mL) and brine (30 mL)
  3. customdry
  4. filtrationfilter
  5. concentrationconcentrate
  6. customPurify the crude material by flash chromatography

Sources & evidence

ORD record
ord-2d4c7434a9734cf3b7a120b84b1c9e34
Source dataset
uspto-grants-2011_03
Patent number
US07902356B2

Reaction notes

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