Ethanol → 3-{[(4-{[Cyclopentyl(3-methyl-1-benzothiophen-2-yl)methyl]amino}phenyl)carbonyl](methyl)amino}propanoic acid

HRID 2091084Notes

Reaction equation

HRID 2091084 reaction equation
[CH:1]1([CH:6]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([N:26]([CH3:34])[CH2:27][CH2:28][C:29]([O:31]CC)=[O:30])=[O:25])=[CH:20][CH:19]=2)[C:7]2[S:8][C:9]3[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=3[C:11]=2[CH3:12])[CH2:5][CH2:4][CH2:3][CH2:2]1.CCCCCC.C(O)C.C(O)C.[OH-].[Na+]>O1CCCC1>[CH:1]1([CH:6]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([N:26]([CH3:34])[CH2:27][CH2:28][C:29]([OH:31])=[O:30])=[O:25])=[CH:20][CH:19]=2)[C:7]2[S:8][C:9]3[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=3[C:11]=2[CH3:12])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 702EthanolHCID 14798Sodium HydroxideHCID 21879635Ethanol hexaneHCID 66777428Ethyl 3-{[(4-{[cyclopentyl(3-methyl-1-benzothiophen-2-yl)methyl]amino}phenyl)carbonyl](methyl)amino}propanoate

Product 1

HCID 667777323-{[(4-{[Cyclopentyl(3-methyl-1-benzothiophen-2-yl)methyl]amino}phenyl)carbonyl](methyl)amino}propanoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Ethyl 3-{[(4-{[cyclopentyl(3-methyl-1-benzothiophen-2-yl)methyl]amino}phenyl)carbonyl](methyl)amino}propanoate (19.7 g) synthesized in Example A64(1) was fractionated by high performance liquid chromatography (column: CHIRALPAK AD (50 mm ID×500 mL, manufactured by Daicel Chemical Industries, Ltd., mobile phase: hexane/ethanol (500/500), flow rate: 60 mL/min, column temperature: room temperature). The fraction containing an optically active form having a shorter retention time under the above-mentioned high performance liquid chromatography conditions was concentrated to give an amorphous form (8.75 g, 99.9% ee). To a mixture of the obtained amorphous form, ethanol (100 mL) and tetrahydrofuran (100 mL) was added 1N aqueous sodium hydroxide solution (30 mL), and the mixture was stirred at room temperature for 5 hr and concentrated under reduced pressure. The residue was dissolved in water (200 mL), and 1N hydrochloric acid (30 mL) was added at 0° C., and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to give the title object compound (7.54 g, 41%, 99.9% ee) as a white solid. The obtained solid was recrystallized from ethanol/water to give colorless crystals.

Workup

  1. additionThe fraction containing an optically active form
  2. concentrationwas concentrated
  3. customto give an amorphous form (8.75 g, 99.9% ee)
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in water (200 mL)
  6. addition1N hydrochloric acid (30 mL) was added at 0° C.
  7. extractionthe mixture was extracted with ethyl acetate
  8. washThe extract was washed with saturated brine
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customto give the title object compound (7.54 g, 41%, 99.9% ee) as a white solid
  12. customThe obtained solid was recrystallized from ethanol/water
  13. customto give colorless crystals

Sources & evidence

ORD record
ord-1a5c69849382447998c6e97c69e1e8ec
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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