Lithium Hydroxide → (S)-3-(4-((2-(4-Butylphenyl)-4-methylthiazol-5-yl)methoxy)phenyl)-3-(4,5-dihydroisoxazol-3-yl)propanoic acid

HRID 1675249Notes

Reaction equation

HRID 1675249 reaction equation
[C:1](=[O:4])([O-])[O-:2].[Cs+].[Cs+].C([C@H]1COC(=O)N1C(=O)[CH2:21][C@@H:22]([C:28]1[CH:33]=[CH:32][C:31]([OH:34])=[CH:30][CH:29]=1)[CH:23]1[CH:27]=[CH:26][O:25][NH:24]1)C1C=CC=CC=1.Cl.[CH2:37]([C:41]1[CH:46]=[CH:45][C:44]([C:47]2[S:48][C:49]([CH2:53]Cl)=[C:50]([CH3:52])[N:51]=2)=[CH:43][CH:42]=1)[CH2:38][CH2:39][CH3:40].[Li+].[OH-]>CS(C)=O.O>[CH2:37]([C:41]1[CH:42]=[CH:43][C:44]([C:47]2[S:48][C:49]([CH2:53][O:34][C:31]3[CH:30]=[CH:29][C:28]([C@@H:22]([C:23]4[CH2:27][CH2:26][O:25][N:24]=4)[CH2:21][C:1]([OH:2])=[O:4])=[CH:33][CH:32]=3)=[C:50]([CH3:52])[N:51]=2)=[CH:45][CH:46]=1)[CH2:38][CH2:39][CH3:40]

Participants

7

Reactant 4

HCID 3939Lithium HydroxideHCID 10796Cesium carbonateHCID 67329489(S)-4-Benzyl-3-((S)-3-(4-hydroxyphenyl)-3-(dihydroisoxazol-3-yl)propanoyl)oxazolidin-2-oneHCID 673310682-(4-Butylphenyl)-5-(chloromethyl)-4-methylthiazole hydrochloride

Product 1

HCID 59252182(S)-3-(4-((2-(4-Butylphenyl)-4-methylthiazol-5-yl)methoxy)phenyl)-3-(4,5-dihydroisoxazol-3-yl)propanoic acidYield 80%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

Cesium carbonate (64 mg, 0.2 mmol) was added to a mixture of 9.2 (6.1 mg, 0.015 mmol) and 2-(4-butylphenyl)-5-(chloromethyl)-4-methylthiazole hydrochloride (14.1) (6 mg, 0.018 mmol) in DMSO (0.5 mL). The mixture was stirred at room temperature for 3 hours. To the reaction mixture was added LiOH in water (0.5 mL, 1 N solution), and the mixture was stirred at 50° C. for 3 hours. The mixture was filtered and purified by reverse phase HPLC to give 14 (6 mg, 0.012 mmol) after lyophilization. MS ESI (pos.) m/e 479.2 (M+H). 1H NMR (500 MHz, CDCl3) δ ppm 7.84 (2 H, d, J=8.3 Hz), 7.32 (2 H, d, J=8.1 Hz), 7.25 (2 H, d, J=8.6 Hz), 6.97 (2 H, d, J=8.8 Hz), 5.20 (2 H, s), 4.31-4.35 (1 H, m), 4.23-4.29 (1 H, m), 4.10 (1 H, t, J=8.1 Hz), 3.28 (1 H, dd, J=16.4, 7.8 Hz), 2.82-2.90 (2 H, m), 2.73-2.77 (1 H, m), 2.69 (2 H, t, J=7.8 Hz), 2.53 (3 H, s), 1.62-1.68 (2 H, m), 1.36-1.42 (2 H, m), 0.96 (3 H, t, J=7.3 Hz)

Workup

  1. stirringthe mixture was stirred at 50° C. for 3 hours
  2. filtrationThe mixture was filtered
  3. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-b20884ffffe54a93a5edaf1f068089da
Source dataset
uspto-grants-2011_08
Patent number
US08003648B2

Reaction notes

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