Diisopropylethylamine → N-{(1S)-1-[(4-Bromophenyl)methyl]-3-hydroxypropyl)-3-cyano-4-[(1-methylethyl)oxy]benzamide
Reaction equation
Cl.[NH2:2][C@@H:3]([CH2:7][C:8]1[CH:13]=[CH:12][C:11]([Br:14])=[CH:10][CH:9]=1)[CH2:4][CH2:5][OH:6].C(N(CC)C(C)C)(C)C.[C:24]([C:26]1[CH:27]=[C:28]([CH:32]=[CH:33][C:34]=1[O:35][CH:36]([CH3:38])[CH3:37])[C:29](O)=[O:30])#[N:25].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Br:14][C:11]1[CH:10]=[CH:9][C:8]([CH2:7][C@H:3]([NH:2][C:29](=[O:30])[C:28]2[CH:32]=[CH:33][C:34]([O:35][CH:36]([CH3:38])[CH3:37])=[C:26]([C:24]#[N:25])[CH:27]=2)[CH2:4][CH2:5][OH:6])=[CH:13][CH:12]=1Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
To a suspension of (3S)-3-Amino-4-(4-bromophenyl)-1-butanol hydrochloride (1.80 g, 6.42 mmol) in dry DMF (32 mL) was added N,N-diisopropylethyl amine (2.49 g, 19.3 mmol) and the resultant clear solution was stirred for 3 min. 3-Cyano-4-[(1-methylethyl)oxy]benzoic acid (1.45 g, 7.06 mmol) and HBTU (2.68 g, 7.06 mmol) were added and the reaction was stirred at rt under nitrogen. After 1.5 h, the reaction mixture was quenched with water (50 mL) and extracted with EtOAc (3×30 mL). The extracts were dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (75% EtOAc/hexanes) to give 2.18 g (78%) of the title compound as a white solid. LC/MS (ES) m/e 431.2 (M+H)+.
Workup
- stirringthe reaction was stirred at rt under nitrogen
- waitAfter 1.5 h
- customthe reaction mixture was quenched with water (50 mL)
- extractionextracted with EtOAc (3×30 mL)
- dry with materialThe extracts were dried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customThe residue was purified by silica gel chromatography (75% EtOAc/hexanes)
Sources & evidence
- ORD record
- ord-35cc2b71975b4c0fadbc9adf9f0a46e0
- Source dataset
- uspto-grants-2014_07
- Patent number
- US08772507B2
Reaction notes
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