Ethanol → HCID 66777843, compound

HRID 2091074Notes

Reaction equation

HRID 2091074 reaction equation
[CH:1]1([CH:7]([NH:18][C:19]2[CH:20]=[CH:21][C:22]([C:25]([N:27]([CH3:35])[CH2:28][CH2:29][C:30]([O:32]CC)=[O:31])=[O:26])=[N:23][CH:24]=2)[C:8]2[S:9][C:10]3[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=3[C:12]=2[CH3:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CCCCCC.CC(O)C.C(O)C.[OH-].[Li+]>O1CCCC1>[CH:1]1([CH:7]([NH:18][C:19]2[CH:20]=[CH:21][C:22]([C:25]([N:27]([CH3:35])[CH2:28][CH2:29][C:30]([OH:32])=[O:31])=[O:26])=[N:23][CH:24]=2)[C:8]2[S:9][C:10]3[CH:17]=[CH:16][CH:15]=[CH:14][C:11]=3[C:12]=2[CH3:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 702EthanolHCID 3939Lithium HydroxideHCID 21585144Isopropanol hexaneHCID 66777349HCID 66777349, compound

Product 1

HCID 66777843HCID 66777843, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Ethyl 3-{[(5-{[cyclohexyl(3-methyl-1-benzothiophen-2-yl)methyl]amino}pyridin-2-yl)carbonyl](methyl)amino}propanoate (9.31 g) synthesized in Example A59(3) was fractionated by high performance liquid chromatography (column: CHIRALPAK AD (50 mm ID×500 mL, manufactured by Daicel Chemical Industries, Ltd., mobile phase: hexane/2-propanol (700/300-200/800), flow rate: 60 mL/min-50 mL/min, column temperature: room temperature). The fraction containing an optically active form having a longer retention time under the above-mentioned high performance liquid chromatography conditions was concentrated to give an amorphous form (4.52 g, 99.9% ee). To a mixture of the obtained amorphous form, ethanol (20 mL) and tetrahydrofuran (20 mL) was added 1N lithium hydroxide aqueous solution (20 mL), and the mixture was stirred at room temperature for 1 hr and concentrated under reduced pressure. The residue was dissolved in water (20 mL), and 1N hydrochloric acid (20 mL) was added at 0° C. The resulting precipitate was collected by filtration to give the title object compound (4.12 g, 98%, 99.9% ee) as a white solid.

Workup

  1. additionThe fraction containing an optically active form
  2. concentrationwas concentrated
  3. customto give an amorphous form (4.52 g, 99.9% ee)
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in water (20 mL)
  6. addition1N hydrochloric acid (20 mL) was added at 0° C
  7. filtrationThe resulting precipitate was collected by filtration
  8. customto give the title object compound (4.12 g, 98%, 99.9% ee) as a white solid

Sources & evidence

ORD record
ord-97b156eb7ada4fbe93261754ed4086d9
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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