Dichloromethane → (E)-3-(6-Amino-5-piperidin-1-ylmethyl-pyridin-3-yl)acrylic acid hydrochloride
Reaction equation
C([O:5][C:6](=[O:23])[CH:7]=[CH:8][C:9]1[CH:10]=[N:11][C:12]([NH2:22])=[C:13]([CH2:15][N:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[CH:14]=1)(C)(C)C.C(O)(C(F)(F)F)=O.C(Cl)[Cl:32]>>[ClH:32].[NH2:22][C:12]1[N:11]=[CH:10][C:9](/[CH:8]=[CH:7]/[C:6]([OH:23])=[O:5])=[CH:14][C:13]=1[CH2:15][N:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1Participants
Procedure
A suspension of 3-(6-amino-5-piperidin-1-ylmethyl-pyridin-3-yl)acrylic acid tert-butyl ester (250 mg, 0.79 mmol) in CH2Cl2 (3 mL) was treated with TFA (2 mL). After stirring at room temperature under N2 for 45 min, the solution was concentrated. The resulting oil was treated with anhydrous HCl in dioxane (10 mL, 4.0 M) and then sonicated until the oil was converted to a fine off-white solid. After stirring under N2 for 20 min, the solid was isolated by filtration, washed with Et2O, and dried under vacuum for several hours to give the title compound (282 mg, quantitative) as an off-white solid: 1H NMR (300 MHz, DMSO-d6) δ 10.6 (br s, 1H), 8.53 (d, J=2.1 Hz, 1H), 8.39-8.28 (m, 3H), 7.53 (d, J=15.0 Hz, 1H), 6.46 (d, J=15.0 Hz, 1H), 4.33 (s, 2H), 3.43-3.35 (m, 2H), 2.97 (s, 2H), 1.79-1.69 (m, 5H), 1.35 (s, 1H).
Workup
- concentrationthe solution was concentrated
- additionThe resulting oil was treated with anhydrous HCl in dioxane (10 mL, 4.0 M)
- customsonicated until the oil
- stirringAfter stirring under N2 for 20 min
- customthe solid was isolated by filtration
- washwashed with Et2O
- customdried under vacuum for several hours
Sources & evidence
- ORD record
- ord-a6ab99b5b0964b34a0545038d4d12b27
- Source dataset
- uspto-grants-2011_02
- Patent number
- US07879872B2
Reaction notes
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