Acetic Acid → 1-(5-chloropyrimidin-2-yl)-N-cyclopropylpiperidin-4-amine
Reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[CH:15]1([NH2:18])[CH2:17][CH2:16]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([NH:18][CH:15]3[CH2:17][CH2:16]3)[CH2:10][CH2:9]2)=[N:6][CH:7]=1Participants
Procedure
1-(5-Chloropyrimidin-2-yl)piperidin-4-one (1.5 g) is dissolved in anhydrous dichloromethane (25 mL) and cyclopropylamine (0.42 g) is added followed by glacial acetic acid (0.80 mL). Sodium triacetoxyborohydride (1.8 g) is added in one portion under nitrogen atmosphere and the resulting mixture is stirred at room temperature for 17 h. The mixture is diluted with dichloromethane (25 mL) and extracted with 3 M aqueous HCl (75 mL and 50 mL). The combined HCl layers are cooled on ice and 4 M aqueous NaOH solution (100 mL) is added in portions until the mixture is strongly basic (pH˜14). The mixture is extracted with dichloromethane (150 mL and 100 mL) and the combined organic layers are dried over Na2SO4, filtered and concentrated to yield the title compound.
Workup
- extractionextracted with 3 M aqueous HCl (75 mL and 50 mL)
- temperatureThe combined HCl layers are cooled on ice and 4 M aqueous NaOH solution (100 mL)
- additionis added in portions until the mixture
- extractionThe mixture is extracted with dichloromethane (150 mL and 100 mL)
- dry with materialthe combined organic layers are dried over Na2SO4
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-28cc83bc354d43b49d93ff6c3724d679
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08822471B2
Reaction notes
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