Reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([CH2:12][C:13]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)=[O:14])[C:9]([OH:11])=O)=[CH:4][CH:3]=1.[NH2:21][C@@H:22]([CH:25]([CH3:27])[CH3:26])[CH2:23][OH:24].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>C(Cl)Cl.CCCCCC.CCOC(C)=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C@H:8]([CH2:12][C:13]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)=[O:14])[C:9]([NH:21][C@H:22]([CH2:23][OH:24])[CH:25]([CH3:27])[CH3:26])=[O:11])=[CH:6][CH:7]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Procedure
2-(S)-(4-Fluoro-phenyl)-4-morpholin-4-yl-4-oxo-butyric acid (2.00 g, 7.11 mmol, 1.0 eq.), 2-(S)-Amino-3-methyl-butan-1-ol (1.59 g, 7.33 mmol, 1.03 eq.) and HATU (2.41 g, 7.33 mmol, 1.03 mmol) were dissolved in CH2Cl2 and stirred at room temperature. Diisopropylethylamine (3.9 mL, 21.98 mmol, 3.1 eq.) was added via syringe and the reaction is monitored by LC/MS. Upon completion, there reaction was evaporated and is diluted with ethyl acetate (100 mL) and extracted with 0.5M HCl (2×30 mL), saturated NaHCO3, and brine. The organic layer is dried over MgSO4, filtered and evaporated. Column chromatography (0-100%) EtOAc in hexane gradient provided 2-(S)-(4-Fluoro-phenyl)-N-(1-(S)-hydroxymethyl-2-methyl-propyl)-4-morpholin-4-yl-4-oxo-butyramide as a clear oil (1.06 g, 2.89 mmol, 41%). HPLC-MS calcd. for C19H27FN2O4 (M+H+) 367.2, found 367.4; TLC (1:1 hexane/EtOAc) Rf=0.15.
Workup
- customUpon completion, there reaction
- customwas evaporated
- additionis diluted with ethyl acetate (100 mL)
- extractionextracted with 0.5M HCl (2×30 mL), saturated NaHCO3, and brine
- dry with materialThe organic layer is dried over MgSO4
- filtrationfiltered
- customevaporated
Sources & evidence
- ORD record
- ord-c742906c4d0441f186bd0d9a5f0ae671
- Source dataset
- uspto-grants-2010_06
- Patent number
- US07732449B2
Linked notes
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