Water → (E)-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)-1-(5-morpholin-4-yl-indan-1-yl)piperidin-2-one

HRID 1362699Notes

Reaction equation

HRID 1362699 reaction equation
CN(C=O)C.[N:6]1([C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[CH:17]([NH:21][C:22](=[O:43])/[C:23](=[CH:28]/[C:29]2[CH:34]=[CH:33][C:32]([N:35]4[CH:39]=[C:38]([CH3:40])[N:37]=[CH:36]4)=[C:31]([O:41][CH3:42])[CH:30]=2)/[CH2:24][CH2:25][CH2:26]Cl)[CH2:16][CH2:15]3)[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1.[H-].[Na+].O>C(OCC)(=O)C>[CH3:42][O:41][C:31]1[CH:30]=[C:29]([CH:34]=[CH:33][C:32]=1[N:35]1[CH:39]=[C:38]([CH3:40])[N:37]=[CH:36]1)/[CH:28]=[C:23]1/[C:22](=[O:43])[N:21]([CH:17]2[C:18]3[C:14](=[CH:13][C:12]([N:6]4[CH2:7][CH2:8][O:9][CH2:10][CH2:11]4)=[CH:20][CH:19]=3)[CH2:15][CH2:16]2)[CH2:26][CH2:25][CH2:24]/1

Participants

6

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 66960274(E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid (5-morpholin-4-yl-indan-1-yl)amide

Product 1

HCID 59170680(E)-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)-1-(5-morpholin-4-yl-indan-1-yl)piperidin-2-oneYield 81.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a DMF (5.0 mL) solution of ((E)-5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid (5-morpholin-4-yl-indan-1-yl)amide (2.80 g), sodium hydride (40% mineral oil content, 267 mg) was added at 0° C., and the reaction solution was agitated for 15 minutes. Water and ethyl acetate were added to the reaction solution after confirming disappearance of the starting materials, and the organic layer was partitioned. After the organic layer was washed with a saturated saline solution, it was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. By purifying the obtained residue by silica gel chromatography (elution solvent: a heptane-ethyl acetate system, ethyl acetate-ethanol system), 2.12 g of (E)-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)-1-(5-morpholin-4-yl-indan-1-yl)piperidin-2-one racemate was obtained. Next, this compound (140 mg) was separated in CHRIALPAK™ AD-H available from Daicel Chemical Industries, Ltd. (2 cm×25 cm mobile phase; ethanol), and the title optically active substance with a retention time of 14 minutes (64 mg; >99% ee) and the title optically active substance with a retention time of 16 minutes (58 mg; >97% ee) were obtained. The physical properties of the title optically active substance with a retention time of 14 minutes are as follows.

Workup

  1. customthe organic layer was partitioned
  2. washAfter the organic layer was washed with a saturated saline solution, it
  3. dry with materialwas dried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customBy purifying the obtained residue by silica gel chromatography (
  6. washelution solvent

Sources & evidence

ORD record
ord-d4b0b9f2156d4f839dc5a47054c0d154
Source dataset
uspto-grants-2011_02
Patent number
US07880009B2

Reaction notes

Loading…