(2S)-2-amino-3-(2-nitrophenyl)propanoic acid → (3S)-3-Amino-3,4-dihydro-1-hydroxy-2(1H)-quinolinone
Reaction equation
[CH:1]1[CH:6]=[C:5]([CH2:7][C@H:8]([NH2:12])[C:9](O)=[O:10])[C:4]([N+:13]([O-:15])=O)=[CH:3][CH:2]=1>CO.O.Cl.[Pt]>[NH2:12][C@H:8]1[CH2:7][C:5]2[C:4](=[CH:3][CH:2]=[CH:1][CH:6]=2)[N:13]([OH:15])[C:9]1=[O:10]Participants
Procedure
L-2-Nitrophenylalanine (C11) (419.6 mg, 2.0 mmol) was dissolved in methanol (23.8 mL) and water (240 μL). Concentrated aqueous HCl (2-4 drops) was added to aid solubility. Platinum on carbon (42 mg) was added and the reaction was hydrogenated on a Parr shaker at 10 psi for 1 hour, whereupon the reaction was filtered through Celite. The catalyst was washed with a 1 N solution of ammonium hydroxide in methanol and then with methanol. The filtrate was concentrated to provide a crude product, which was subsequently dry packed with a minimum amount of silica, using a methanol/dichloromethane solution to dissolve the material. Purification using silica gel chromatography (Gradient: 0% to 20% methanol (containing 1% ammonium hydroxide) in dichloromethane) provided Example 4 as a solid (207 mg, 58%). APCI m/z 179.1 (M+1). 1H NMR (400 MHz, CD3OD) δ 2.88 (dd, J=14, 15 Hz, 1H), 3.09 (dd, J=15.3, 6.2 Hz, 1H), 3.67 (dd, J=13.6, 6.1 Hz, 1H,) 7.06 (ddd, J=7.2, 7.2, 1.7 Hz, 1H), 7.23 (br d, J=7.5 Hz, 1H), 7.27-7.34 (m, 2H).
Workup
- filtrationwas filtered through Celite
- washThe catalyst was washed with a 1 N solution of ammonium hydroxide in methanol
- concentrationThe filtrate was concentrated
- customto provide a crude product, which
- customwas subsequently dry
- dissolutionto dissolve the material
- customPurification
Sources & evidence
- ORD record
- ord-6ec660c712fa4e3a81c000ff65e8d9a8
- Source dataset
- uspto-grants-2013_07
- Patent number
- US08487104B2
Reaction notes
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