Ethanol → tert-butyl 4-[(4-cyanopiperidin-1-yl)methyl]tetrahydro-2H-pyran-4-carboxylate
Reaction equation
[C:1]([O:5][C:6]([C:8]1([CH2:14][N:15]2[CH2:20][CH2:19][C:18](=O)[CH2:17][CH2:16]2)[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(C)C=CC(S([CH2:31][N+:32]#[C-])(=O)=O)=CC=1.C(O)C.CC(C)([O-])C.[K+].C([O-])(O)=O.[Na+]>COCCOC>[C:31]([CH:18]1[CH2:17][CH2:16][N:15]([CH2:14][C:8]2([C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH2:20][CH2:19]1)#[N:32]Participants
7
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 50 °C
Procedure
To a stirred solution of tert-butyl-4-[(4-oxopiperidin-1-yl)methyl]tetra hydro-2H-pyran-4-carboxylate (8.77 g, 0.0295 mol, step 3 of Example 3) in 1,2-dimethoxyethane (250 mL) was added p-toluenesulfonylmethylisocyanide (11.51 g, 0.0590 mol), ethanol (3.96 mL, 0.0678 mol) and potassium t-butoxide (11.58 g, 0.1032 mol) at 0° C. The resulting mixture was stirred at 50° C. for 16 h. After cooling, the reaction mixture was poured into sat. NaHCO3 aq. (200 mL), and the mixture was extracted with CH2Cl2 (200 mL×3). The extracts were dried over Na2SO4, filtered and concentrated. The residue was chromatographed on a column of silica gel eluting with hexane/ethyl acetate (2:1) to give 5.76 g (63%) of the title compound as yellow syrup.
Workup
- temperatureAfter cooling
- extractionthe mixture was extracted with CH2Cl2 (200 mL×3)
- dry with materialThe extracts were dried over Na2SO4
- filtrationfiltered
- concentrationconcentrated
- customThe residue was chromatographed on a column of silica gel eluting with hexane/ethyl acetate (2:1)
Sources & evidence
- ORD record
- ord-628cff206a524bac94abf53213990332
- Source dataset
- uspto-grants-2009_09
- Patent number
- US07589109B2
Reaction notes
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