Isopropanol → 1-(2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)-3-methylpiperidine-3-carboxylic acid

HRID 1948531Notes

Reaction equation

HRID 1948531 reaction equation
[C:1](=[O:4])([O-])[O-:2].[Cs+].[Cs+].[O:7]1[CH2:9][CH:8]1[C:10]1[CH:15]=[CH:14][C:13]([C:16]2[N:20]=[C:19]([C:21]3[O:25][N:24]=[C:23]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[C:22]=3[C:32]([F:35])([F:34])[F:33])[O:18][N:17]=2)=[CH:12][CH:11]=1.[CH3:36][CH:37](O)[CH3:38]>CS(C)=O>[OH:7][CH:8]([C:10]1[CH:11]=[CH:12][C:13]([C:16]2[N:20]=[C:19]([C:21]3[O:25][N:24]=[C:23]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[C:22]=3[C:32]([F:34])([F:33])[F:35])[O:18][N:17]=2)=[CH:14][CH:15]=1)[CH2:9][N:17]1[CH2:16][CH2:13][CH2:12][C:37]([CH3:38])([C:1]([OH:2])=[O:4])[CH2:36]1

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 10796Cesium carbonateHCID 866563983-(4-(Oxiran-2-yl)phenyl)-5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazole

Product 1

HCID 509238411-(2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)-3-methylpiperidine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of ethyl 3-methylpiperidine-3-carboxylate, HCl (62.4 mg, 0.301 mmol), and cesium carbonate (98 mg, 0.301 mmol) in 2-propanol (2 mL) and DMSO (1 mL) was added 3-(4-(oxiran-2-yl)phenyl)-5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazole, Preparation 28C (30 mg, 0.075 mmol). The reaction mixture was heated at 80° C. overnight. The reaction mixture was filtered and purified by HPLC. HPLC conditions: PHENOMENEX® Luna 5 micron C18 column (30×100 mm); 10% MeOH/water (0.1% TFA)/90% MeOH/water (0.1% TFA); 10%-100% gradient over 15 minutes; 20 mL/min. Fraction with the correct mass were isolated and concentrated in vacuo. The residue was treated with 6N HCl/MeCN for 3 days and purified by HPLC. HPLC conditions: PHENOMENEX® Luna C18 5 micron column (250×30 mm); 25-100% CH3CN/water (0.1% TFA); 25 minute gradient; 30 mL/min. Isolated fractions with correct mass were freeze-dried overnight to yield 1 mg of 1-(2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)-3-methylpiperidine-3-carboxylic acid as a TFA salt. MS (m+1)=543. HPLC Peak RT=3.29 minutes (Analytical Method A). Purity=95%.

Workup

  1. additionwas added
  2. filtrationThe reaction mixture was filtered
  3. custompurified by HPLC
  4. customFraction with the correct mass were isolated
  5. concentrationconcentrated in vacuo
  6. additionThe residue was treated with 6N HCl/MeCN for 3 days
  7. custompurified by HPLC
  8. custom25 minute
  9. customIsolated fractions with correct mass were freeze-dried overnight

Sources & evidence

ORD record
ord-cf4316f73ab1466fb6d51902091690a6
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

Loading…