4-Methylmorpholine → 1-Benzyl-4-(2-(3,3,3-trifluoropropanoyl)-amino-4-fluoro--phenylamino)-piperidine
Reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=2N)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:23][C:24]([F:30])([F:29])[CH2:25][C:26](O)=[O:27].C[N:32]1CCOCC1>ClCCl.C(OCC)(=O)C>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([NH2:32])[C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=2[C:26](=[O:27])[CH2:25][C:24]([F:30])([F:29])[F:23])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1Participants
6
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Procedure
To a solution of 9.1 g 1-Benzyl-4-(2-amino-4-fluoro-phenylamino)-piperidine, 2.7 ml 3,3,3-trifluoropropionic acid and 18.6 ml N-methyl-morpholine in 350 ml dichloromethane was dropped 36.4 ml of a 50% solution of PPA in ethyl acetate. The mixture was stirred for 12 h at r.t., extracted 3× with 250 ml water, and the aqueous layers were extracted with 150 ml dichloromethane. After drying the combined organic layers with MgSO4, the solution was evaporated and purified by flash chromatography with dichloromethane/methanol 19:1. The yield was 11.9 g of the desired product.
Workup
- extractionextracted 3× with 250 ml water
- extractionthe aqueous layers were extracted with 150 ml dichloromethane
- dry with materialAfter drying the combined organic layers with MgSO4
- customthe solution was evaporated
- custompurified by flash chromatography with dichloromethane/methanol 19:1
Sources & evidence
- ORD record
- ord-ef320d2ce6af4508b33a29c5fa479849
- Source dataset
- uspto-grants-2007_01
- Patent number
- US07157471B2
Reaction notes
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