Water → HCID 66961556, compound

HRID 1446600Notes

Reaction equation

HRID 1446600 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:12]=[C:11]2[C:7]([CH2:8][CH2:9][CH:10]2[NH:13][C:14](=[O:35])/[C:15](=[CH:20]/[C:21]2[CH:26]=[CH:25][C:24]([N:27]3[CH:31]=[C:30]([CH3:32])[N:29]=[CH:28]3)=[C:23]([O:33][CH3:34])[CH:22]=2)/[CH2:16][CH2:17][CH2:18]Cl)=[CH:6][C:5]=1[N:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1.O.C(OCC)(=O)C>CN(C=O)C>[F:3][C:4]1[CH:12]=[C:11]2[C:7]([CH2:8][CH2:9][CH:10]2[N:13]2[CH2:18][CH2:17][CH2:16]/[C:15](=[CH:20]\[C:21]3[CH:26]=[CH:25][C:24]([N:27]4[CH:31]=[C:30]([CH3:32])[N:29]=[CH:28]4)=[C:23]([O:33][CH3:34])[CH:22]=3)/[C:14]2=[O:35])=[CH:6][C:5]=1[N:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 66960276HCID 66960276, compound

Product 1

HCID 66961556HCID 66961556, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (containing mineral oil at 40%, 19.0 mg) was added to a solution of (E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid (6-fluoro-5-morpholin-4-ylindan-1-yl)amide (123 mg) in DMF (3.0 mL) at 0° C., and the reaction solution was stirred for 15 minutes. After confirming that the raw materials disappeared, water and ethyl acetate were added to the reaction solution and the organic layer was partitioned. The organic layer was washed with brine, and then dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (elution solvent:heptane-ethyl acetate system, ethyl acetate-methanol system) to obtain 85 mg of (E)-1-(6-fluoro-5-morpholin-4-ylindan-1-yl)-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)piperidin-2-one as a racemate. Next, the compound (12.0 mg) was fractionated using CHIRALCEL™ OD-H manufactured by Daicel Chemical Industries, Ltd. (2 cm×25 cm: mobile phase: hexane:ethanol=70:30) to obtain the title optically active substance with a retention time of 13 minutes (Example 973, 4.60 mg; >99% ee) and the title optically active substance with a retention time of 15 minutes (Example 974, 4.70 mg; >99% ee). The physical properties of the optically active substances are as follows.

Workup

  1. customthe organic layer was partitioned
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by silica gel chromatography (elution solvent:heptane-ethyl acetate system, ethyl acetate-methanol system)

Sources & evidence

ORD record
ord-454b3dd0febf4283b79ee8bfb1a48fbf
Source dataset
uspto-grants-2010_02
Patent number
US07667041B2

Reaction notes

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