Lithium Hydroxide → (S)-3-(4-(3,4-Bis(trifluoromethoxy)benzyloxy)phenyl)-3-(isoxazol-3-yl)propanoic acid
Reaction equation
[C:1](=[O:4])([O-])[O-:2].[Cs+].[Cs+].Br[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[C:11]([O:20][C:21]([F:24])([F:23])[F:22])[CH:10]=1.C([C@H]1COC(=O)N1C(=O)[CH2:39][C@@H:40]([C:46]1[CH:51]=[CH:50][C:49]([OH:52])=[CH:48][CH:47]=1)[C:41]1[CH:45]=[CH:44][O:43][N:42]=1)C1C=CC=CC=1.[Li+].[OH-]>CN(C=O)C.O.C1COCC1>[F:22][C:21]([F:24])([F:23])[O:20][C:11]1[CH:10]=[C:9]([CH:14]=[CH:13][C:12]=1[O:15][C:16]([F:19])([F:18])[F:17])[CH2:8][O:52][C:49]1[CH:48]=[CH:47][C:46]([C@@H:40]([C:41]2[CH:45]=[CH:44][O:43][N:42]=2)[CH2:39][C:1]([OH:2])=[O:4])=[CH:51][CH:50]=1Participants
8
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Procedure
Cesium carbonate (137 mg, 0.4 mmol) was added to a mixture of 4-(bromomethyl)-1,2-bis(trifluoromethoxy)benzene 22.1 (71 mg, 0.21 mmol) and 7.5 (82 mg, 0.21 mmol) in DMF (2 mL). The mixture was stirred at room temperature for 16 hours. To the reaction mixture was added LiOH in water (0.5 mL, 1N solution) and THF (1 mL). The mixture was stirred at 23° C. for 3 hours. The mixture was filtered and purified by reverse phase HPLC to give 22 (19 mg) after lyophilization. MS ESI (pos.) m/e 492.1 (M+H). 1H NMR (400 MHz, CDCl3) δ 8.31 (1 H, s), 7.45 (1 H, s), 7.39 (2 H, s), 7.21 (2 H, d, J=8.3 Hz), 6.93 (2 H, d, J=8.8 Hz), 6.08 (1 H, s), 5.05 (2 H, s), 4.57 (1 H, t, J=7.6 Hz), 3.37 (1 H, dd, J=16.6, 7.8 Hz), 3.00 (1 H, dd, J=16.6, 7.8 Hz).
Workup
- stirringThe mixture was stirred at 23° C. for 3 hours
- filtrationThe mixture was filtered
- custompurified by reverse phase HPLC
Sources & evidence
- ORD record
- ord-976db3060e2e4a8c848f486e08be173b
- Source dataset
- uspto-grants-2011_08
- Patent number
- US08003648B2
Reaction notes
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