Diisopropylethylamine → 1-[1-(4-Chloro-phenyl)-cyclobutanecarbonyl]-piperidin-3-ylmethyl alcohol
Reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]([CH2:7][OH:8])[CH2:2]1.[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2([C:20](O)=[O:21])[CH2:19][CH2:18][CH2:17]2)=[CH:12][CH:11]=1.C(N(C(C)C)CC)(C)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>ClCCl>[Cl:9][C:10]1[CH:11]=[CH:12][C:13]([C:16]2([C:20]([N:1]3[CH2:6][CH2:5][CH2:4][CH:3]([CH2:7][OH:8])[CH2:2]3)=[O:21])[CH2:19][CH2:18][CH2:17]2)=[CH:14][CH:15]=1Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
To a solution of 3-piperidinemethanol (5.0 g, 43.4 mmol), 1-(4-chlorophenyl)-1-cyclobutanecarboxylic acid (9.14 g, 43.4 mmol), and diisopropylethylamine (11.22 g, 86.8 mmol) in dichloromethane (100 mL) at 0° C. was added PyBroP® (22.26 g, 47.8 mmol). The reaction was stirred at 0° C. for 1 h and then at room temperature for 4 h. The reaction mixture was washed successively with water, 1 N HCl, water, sat. sodium bicarbonate solution, and water (100 mL each). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated by rotary evaporation. The residue was purified by chromatography on silica gel, eluting with dichloromethane/methanol (96:4) to give 5.8 g of the amide 1 as a thick gum.
Workup
- waitat room temperature for 4 h
- washThe reaction mixture was washed successively with water, 1 N HCl, water, sat. sodium bicarbonate solution, and water (100 mL each)
- dry with materialThe organic layer was dried over anhydrous sodium sulfate
- filtrationfiltered
- concentrationconcentrated by rotary evaporation
- customThe residue was purified by chromatography on silica gel
- washeluting with dichloromethane/methanol (96:4)
Sources & evidence
- ORD record
- ord-0a89286097084166ad907101fbf5a093
- Source dataset
- uspto-grants-2005_08
- Patent number
- US06936614B2
Reaction notes
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