Ethyl Acetate → HCID 11718871, compound

HRID 2247617Notes

Reaction equation

HRID 2247617 reaction equation
[H-].[Na+].[CH2:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6][CH2:5][CH:4]1[NH:13][C:14](=[O:35])/[C:15](=[CH:20]/[C:21]1[CH:26]=[CH:25][C:24]([N:27]2[CH:31]=[C:30]([CH3:32])[N:29]=[CH:28]2)=[C:23]([O:33][CH3:34])[CH:22]=1)/[CH2:16][CH2:17][CH2:18]Cl.C(=O)(O)[O-].[Na+].C(OCC)(=O)C>CN(C=O)C>[CH3:34][O:33][C:23]1[CH:22]=[C:21]([CH:26]=[CH:25][C:24]=1[N:27]1[CH:31]=[C:30]([CH3:32])[N:29]=[CH:28]1)/[CH:20]=[C:15]1/[C:14](=[O:35])[N:13]([CH:4]2[CH2:5][CH2:6][C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH2:3]2)[CH2:18][CH2:17][CH2:16]/1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 66960330HCID 66960330, compound

Product 1

HCID 11718871HCID 11718871, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

IPEA (0.58 mL), EDC (0.38 g) and HOBT (0.27 g) were added to a suspension of (E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid trifluoroacetate (300 mg) and 1,2,3,4-tetrahydronaphthalen-2-ylamine (148 mg) in DMF (10 mL) at room temperature, and the reaction solution was stirred at room temperature for 1 hour. A saturated aqueous solution of sodium bicarbonate and ethyl acetate were added to the reaction solution and the organic layer was partitioned. The organic layer was washed sequentially with a saturated aqueous solution of ammonium chloride, water and a saturated aqueous solution of sodium chloride. The organic layer was dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (Carrier: Chromatorex™ NH, elution solvent: heptane-ethyl acetate system) to obtain (E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid (1,2,3,4-tetrahydronaphthalen-2-yl)amide (255 mg). Sodium hydride (containing mineral oil at 40%, 50 mg) was added to a solution of (E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid (1,2,3,4-tetrahydronaphthalen-2-yl)amide (255 mg) in DMF (6 mL) at room temperature, and the reaction solution was stirred at room temperature for 30 minutes. A saturated aqueous solution of sodium bicarbonate and ethyl acetate were added to the reaction solution and the organic layer was partitioned. The organic layer was washed sequentially with a saturated aqueous solution of ammonium chloride, water and a saturated aqueous solution of sodium chloride. The organic layer was dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (Carrier: Chromatorex™ NH, elution solvent: heptane-ethyl acetate system) to obtain (E)-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)-1-(1,2,3,4-tetrahydronaphthalen-2-yl)piperidin-2-one as a racemate (210 mg). The compound (12 mg) was fractionated using CHIRALPAK™ AD-H manufactured by Daicel Chemical Industries, Ltd. (2 cm×25 cm: mobile phase: ethanol) to obtain the title optically active substance with a retention time of 9.5 minutes (Example 1014, 6.0 mg; >99% ee) and the title optically active substance with a retention time of 13.0 minutes (Example 1015, 5.9 mg; >99% ee). The physical properties of the compounds are as follows.

Workup

  1. customthe organic layer was partitioned
  2. washThe organic layer was washed sequentially with a saturated aqueous solution of ammonium chloride, water
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by silica gel chromatography (Carrier: Chromatorex™ NH, elution solvent: heptane-ethyl acetate system)

Sources & evidence

ORD record
ord-0b438f2fae7f4e2186d3bcda94c40aa6
Source dataset
uspto-grants-2010_03
Patent number
US07687640B2

Reaction notes

Loading…