Chloroform → 4-Amino-1-{(2R)-2-((1R)-3,3-difluorocyclopentyl)-2-hydroxy-2-Phenylacetyl}piperidine monohydrochloride
Reaction equation
C(OC([NH:8][CH:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1)=O)(C)(C)C.[F:15][C:16]1([F:32])[CH2:20][CH2:19][C@@H:18]([C@@:21]([OH:31])([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:22](O)=[O:23])[CH2:17]1.ON1C2C=CC=CC=2N=N1.C(N=C=NCCCN(C)C)C.C(Cl)(Cl)[Cl:55]>C(OCC)(=O)C>[ClH:55].[NH2:8][CH:9]1[CH2:10][CH2:11][N:12]([C:22](=[O:23])[C@:21]([C@@H:18]2[CH2:19][CH2:20][C:16]([F:15])([F:32])[CH2:17]2)([OH:31])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:13][CH2:14]1Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of 220 mg of 4-t-butoxycarbonylaminopiperidine and 256 mg of (2R)-2-((1R)-3, 3-difluorocyclopentyl)-2-hydroxy-2-phenylacetic acid in 8 ml of chloroform, 203 mg of 1-hydroxybenzotriazole and 201 mg of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide were added sequentially at room temperature, followed by stirring for 3 hours at the same temperature. The reaction mixture was diluted with ethyl acetate and, after sequential washing with an aqueous solution of 1N sodium hydroxide and brine, dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and 314 mg of the title compound was obtained by purifying the resultant residue by silica gel column chromatography (eluting solvent: hexane/ethyl acetate=2/1).
Workup
- washafter sequential washing with an aqueous solution of 1N sodium hydroxide and brine
- dry with materialdried over anhydrous sodium sulfate
- distillationThe solvent was distilled off under reduced pressure
Sources & evidence
- ORD record
- ord-3aacc474d660469a9c8f25a07ba6857a
- Source dataset
- uspto-grants-2000_10
- Patent number
- US06140333
Reaction notes
Loading…