Reaction equation
CO.[NH2:3][OH:4].[C-]#N.[K+].[C:8](O)(=O)[CH2:9][C:10]([CH2:15][C:16]([OH:18])=O)(C(O)=O)O.[CH2:21]1[CH2:25]O[CH2:23][CH2:22]1>>[OH:4][NH:3][C:16](=[O:18])[CH2:15][CH2:10][C:9]1[CH:8]=[CH:25][CH:21]=[CH:22][CH:23]=1Participants
Procedure
To methyl 3-phenyl propionate (0.328 g, 2.0 mmol) in THF:MeOH:50% aqueous NH2OH (1:1:0.5, 2.5 mL) was added KCN (5 mg, 0.08 mmol, 4 mol %)) and the mixture was stirred at ambient temperature. After 3 h the reaction was complete by HPLC and saturated aqueous citric acid was added (25 mL) followed by extraction with EtOAc (3×25 mL). The organic phase was isolated, dried (MgSO4), filtered, and the filtrate was concentrated in vacuo to give a residue. The residue was purified by reverse phase HPLC (C-18, 5μ 100×30 mm column), eluting with a gradient of acetonitrile: water (0.05% TFA). Following lyophilization of the product fractions there was obtained pure N-hydroxy-3-phenylpropionamide (IIc) as a fluffy solid (0.220 g, 67% yield): LRMS (M+H)+: 166.0 m/z; 1H NMR (DMSO-d6) δ: 10.31(s, 1H), 8.68(br, 1H), 7.17(m, 5H), 2.79(t, 2H), 2.21(t, 2H); Anal (C,H,N): % C (calc) 65.44, (found) 65.38; % H (calc.) 6.71, (found) 6.61; % N (calc.) 8.48, (found) 8.08.
Workup
- additionwas added (25 mL)
- extractionfollowed by extraction with EtOAc (3×25 mL)
- customThe organic phase was isolated
- dry with materialdried (MgSO4)
- filtrationfiltered
- concentrationthe filtrate was concentrated in vacuo
- customto give a residue
- customThe residue was purified by reverse phase HPLC (C-18, 5μ 100×30 mm column)
- washeluting with a gradient of acetonitrile
Sources & evidence
- ORD record
- ord-5b76ebe2f85c4797a129d4a766435beb
- Source dataset
- uspto-grants-2006_08
- Patent number
- US07091378B2
Linked notes
Loading…