4-Piperidinemethanol → Ethyl 6-(allyloxy)-5-(benzyloxy)-2-(4-(hydroxymethyl)piperidin-1-yl)pyrimidine-4-carboxylate

HRID 1093116Notes

Reaction equation

HRID 1093116 reaction equation
[CH2:1]([O:4][C:5]1[N:10]=[C:9](S(C)(=O)=O)[N:8]=[C:7]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:6]=1[O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH:2]=[CH2:3].[NH:28]1[CH2:33][CH2:32][CH:31]([CH2:34][OH:35])[CH2:30][CH2:29]1>C1COCC1.C(OCC)(=O)C>[CH2:1]([O:4][C:5]1[N:10]=[C:9]([N:28]2[CH2:33][CH2:32][CH:31]([CH2:34][OH:35])[CH2:30][CH2:29]2)[N:8]=[C:7]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:6]=1[O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH:2]=[CH2:3]

Participants

5

Reactant 2

HCID 4207714-PiperidinemethanolHCID 57905117Ethyl 6-(allyloxy)-5-(benzyloxy)-2-(methylsulfonyl)pyrimidine-4-carboxylate

Product 1

HCID 57904733Ethyl 6-(allyloxy)-5-(benzyloxy)-2-(4-(hydroxymethyl)piperidin-1-yl)pyrimidine-4-carboxylateYield 58%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

A solution of ethyl 6-(allyloxy)-5-(benzyloxy)-2-(methylsulfonyl)pyrimidine-4-carboxylate (1.911 g, 4.87 mmol) in THF (40 mL) was stirred with molecular sieves for 30 min. To this mixture was added piperidin-4-ylmethanol (1.683 g, 14.61 mmol) and the resulting mixture was stirred overnight at 70° C. The mixture was cooled to room temperature and diluted with ethyl acetate and washed with water followed by brine then dried (Na2SO4). Filtration followed by concentration gave a yellow oil that was purified by flash column chromatography (Biotage flash chromatography system; 0%-100%, 10 CV) to afford the title compound as a yellow oil (1.2043 g, 58% yield). 1H NMR (300 MHz, CDCl3) δ: 7.42-7.39 (2H, m), 7.35-7.27 (3H, m), 6.10-5.97 (1H, m), 5.42-5.34 (1H, m), 5.28-5.22 (1H, m), 4.91 (2H, s), 4.87-4.84 (2H, m), 4.72-4.63 (2H, m), 4.30 (2H, q, J=7.1 Hz), 3.50 (2H, t, J=5.8 Hz), 2.80 (2H, td, J=12.8, 1.8 Hz), 1.79-1.64 (3H, m), 1.28 (3H, t, J=7.1 Hz), 1.23-1.10 (2H, m).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. washwashed with water
  3. dry with materialthen dried (Na2SO4)
  4. filtrationFiltration
  5. concentrationfollowed by concentration
  6. customgave a yellow oil that
  7. customwas purified by flash column chromatography (Biotage flash chromatography system; 0%-100%, 10 CV)

Sources & evidence

ORD record
ord-70ba3aaf3ebb4c7b936e4fc7e2a2003e
Source dataset
uspto-grants-2012_03
Patent number
US08129398B2

Reaction notes

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