Diisopropylethylamine → 4-[1-(3-Chloro-phenyl)-2-hydroxy-ethylcarbamoyl]-piperazine-1-carboxylic acid tert-butyl ester
Reaction equation
Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].C(N(C(C)C)CC)(C)C.[CH:35]1[CH:40]=[C:39]([Cl:41])[CH:38]=[C:37]([C@H:42]([NH2:45])[CH2:43][OH:44])[CH:36]=1>C(Cl)Cl>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][N:23]([C:2](=[O:4])[NH:45][CH:42]([C:37]2[CH:36]=[CH:35][CH:40]=[C:39]([Cl:41])[CH:38]=2)[CH2:43][OH:44])[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:14])[CH3:15]Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -78 °C
Procedure
Triphosgene (264 mg, 0.89 mmol) was dissolved in methylene chloride (20 mL) and the mixture cooled to −78° C. under nitrogen atmosphere. A mixture of t-butoxycarbonyl-piperazine (500 mg, 2.4 mmol) and diisopropylethylamine (2 mL) in CH2Cl2 was added dropwise to the cold stirring solution over 30 minutes. When the addition was complete, a mixture of (S)-(+)-3-chlorophenylglycinol (500 mg, 2.4 mmol) and DIEA (2 mL) in CH2CL2 (5 mL) was added. The reaction warmed to ambient temperature and concentrated in vacuo. The resulting residue was purified by preparative HPLC (Gilson: Column=CombiHT SB-C189 5 μM 21.2 mm×100 mm, eluent=0.1% TFA MeCN/H2O gradient) to afford the desired compound as a yellow oil (134 mg) Rt=6.72 minutes.
Workup
- additionwas added dropwise to the cold stirring solution over 30 minutes
- additionWhen the addition
- additionwas added
- temperatureThe reaction warmed to ambient temperature
- concentrationconcentrated in vacuo
- customThe resulting residue was purified by preparative HPLC (Gilson: Column=CombiHT SB-C189 5 μM 21.2 mm×100 mm, eluent=0.1% TFA MeCN/H2O gradient)
Sources & evidence
- ORD record
- ord-6463d26336224aa188167b31626e03be
- Source dataset
- uspto-grants-2007_07
- Patent number
- US07244735B2
Reaction notes
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