Ethanol → 3-(Cyclopropylamino)-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylic acid
Reaction equation
[CH:1]1([NH:4][C:5]2C(C#N)=[N:7][CH:8]=[C:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[CH:10]=2)[CH2:3][CH2:2]1.[OH-:21].[Na+].[CH2:23]([OH:25])[CH3:24]>>[CH:1]1([NH:4][C:5]2[C:24]([C:23]([OH:21])=[O:25])=[N:7][CH:8]=[C:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[CH:10]=2)[CH2:3][CH2:2]1Participants
Conditions
- Temperature
- 100 °C
Procedure
A solution of 3-(cyclopropylamino)-5-[(4-fluorophenyl)methyl]-2-pyridinecarbonitrile (360 mg, 1.34 mmol) in ethanol (25 mL) was treated with sodium hydroxide (2 mL, 50% aqueous) and heated at 100° C. (bath temperature) for 14 hours. The reaction mixture was concentrated in vacuo and the residue taken up in water and cooled in an ice bath. The solution was acidified by the slow addition of 6 NHCl (final pH˜3). The aqueous layer was extracted with ethyl acetate and the organics dried over sodium sulfate. Filtration and concentration gave 3-(cyclopropylamino)-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylic acid (385 mg, 99%) as a white powder. 1H NMR (400 MHz, CDCl3) δ 8.94 (br, 1 H), 7.93 (s, 1 H), 7.74 (s, 1 H), 7.30 (s, 1 H), 7.15 (dd, J=8.5, 5.5 Hz, 2 H), 7.00 (t, J=8.7 Hz, 2 H), 3.97 (s, 2 H), 2.40 (m, 1 H), 0.77 (m, 2 H), 0.54 (m, 2 H); MS m/z 287 M+1).
Workup
- concentrationThe reaction mixture was concentrated in vacuo
- temperaturecooled in an ice bath
- additionThe solution was acidified by the slow addition of 6 NHCl (final pH˜3)
- extractionThe aqueous layer was extracted with ethyl acetate
- dry with materialthe organics dried over sodium sulfate
- filtrationFiltration and concentration
Sources & evidence
- ORD record
- ord-63489ddf97944f85a68cdbb92e113b49
- Source dataset
- uspto-grants-2014_04
- Patent number
- US08691991B2
Reaction notes
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