Citric Acid → N-hydroxy-2-phenylacetamide

To methyl phenylacetate (0.288 mL, 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 2 h the reaction was complete by HPLC. To the mixture was added saturated aqueous citric acid (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-2-phenylacetamide as a fluffy solid (0.234 g, 77% yield): LRMS (M+H)+: 152.1 m/z; 1H NMR (DMSO-d6) δ: 10.6(s, 1H), 8.81(s, 1H), 7.2(m, 5H), 3.26(s, 2H); Anal (C,H,N): % C: (calc) 63.56; (found) 63.63; % H: (calc.) 6.00; (found) 5.91; % N: (calc.) 9.27, (found) 9.04.

1. extractionfollowed by extraction with EtOAc (3×25 mL)
2. customThe organic phase was isolated
3. dry with materialdried (MgSO4)
4. filtrationfiltered
5. concentrationthe filtrate was concentrated in vacuo
6. customto give a residue
7. customThe residue was purified by reverse phase HPLC (C-18, 5μ 100×30 mm column)
8. washeluting with a gradient of acetonitrile

ORD record

ord-645a5165719843d689ffc71ed8b89810

Source dataset

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07091378B2