Hydrochloric Acid → 4-{[(2S)-1-methylpyrrolidin-2-yl]methoxy}-2-[tetrahydro-2H-pyran-4-yl(trifluoroacetyl)amino]benzoic acid trifluoroacetate
Reaction equation
[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[CH2:7][O:8][C:9]1[CH:21]=[CH:20][C:12]([C:13]([O:15]C(C)(C)C)=[O:14])=[C:11]([N:22]([CH:29]2[CH2:34][CH2:33][O:32][CH2:31][CH2:30]2)[C:23](=[O:28])[C:24]([F:27])([F:26])[F:25])[CH:10]=1.Cl.[O:36]1CCOCC1>C(Cl)Cl>[F:25][C:24]([F:27])([F:26])[C:23]([OH:28])=[O:36].[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[CH2:7][O:8][C:9]1[CH:21]=[CH:20][C:12]([C:13]([OH:15])=[O:14])=[C:11]([N:22]([CH:29]2[CH2:30][CH2:31][O:32][CH2:33][CH2:34]2)[C:23](=[O:28])[C:24]([F:25])([F:27])[F:26])[CH:10]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
Tert-butyl 4-{[(2S)-1-methylpyrrolidin-2-yl]methoxy}-2-[tetrahydro-2H-pyran-4-yl(trifluoroacetyl)amino]benzoate (480 mg, 1 mmol) was dissolved in 20 ml of DCM. Anhydrous HCl 4M in dioxane was added (2.5 ml, 10 mmol). The reaction was stirred at room temperature for 5 days after that the HPLC analysis showed the formation of the desired product but with almost 30% of the detrifluoroacetylated by-product. Solvents were removed under vacuum and the resulting yellow powder was suspended in 15 ml of DCM and TFAA (0.28 ml, 2 mmol) was added. The solid immediately dissolved and the mixture was stirred for 2 hours after that the HPLC analysis showed the complete disappearance of the by product. Solvents were evaporated to dryness to yield a dark yellow solid which was used in the next synthetic step without any further purification.
Sources & evidence
- ORD record
- ord-f0986073fcd64bf1a9d332dec1e1848f
- Source dataset
- uspto-grants-2014_03
- Patent number
- US08673893B2
Reaction notes
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