Ethanol → HCID 66779060, compound

HRID 2091052Notes

Reaction equation

HRID 2091052 reaction equation
[CH:1]1([CH:7]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]([N:30]([CH3:38])[CH2:31][CH2:32][C:33]([O:35]CC)=[O:34])=[O:29])=[CH:24][CH:23]=2)[C:8]2[O:9][C:10]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:11]=3[C:12]=2[CH2:13][O:14][CH3:15])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CCCCCC.C(O)C.C(O)C.[OH-].[Na+]>O1CCCC1>[CH:1]1([CH:7]([NH:21][C:22]2[CH:23]=[CH:24][C:25]([C:28]([N:30]([CH3:38])[CH2:31][CH2:32][C:33]([OH:35])=[O:34])=[O:29])=[CH:26][CH:27]=2)[C:8]2[O:9][C:10]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:11]=3[C:12]=2[CH2:13][O:14][CH3:15])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 702EthanolHCID 14798Sodium HydroxideHCID 21879635Ethanol hexaneHCID 66778108HCID 66778108, compound

Product 1

HCID 66779060HCID 66779060, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Ethyl 3-[{[4-({cyclohexyl[5-fluoro-3-(methoxymethyl)-1-benzofuran-2-yl]methyl}amino)phenyl]carbonyl}(methyl)amino]propanoate (1.20 g) synthesized in Example A48(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 (200/800), flow rate: 60 mL/min, column temperature: 30° C.). 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 (465 mg, 99.9% ee). To a mixture of the obtained amorphous form, ethanol (5 mL) and tetrahydrofuran (5 mL) was added 1N aqueous sodium hydroxide solution (2.00 mL), and the mixture was stirred at room temperature for 2 hr, and concentrated under reduced pressure. The residue was dissolved in water (10 mL), and 1N hydrochloric acid (2.00 mL) was added at 0° C. The resulting precipitate was collected by filtration to give the title object compound (415 mg, 37%, 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 (465 mg, 99.9% ee)
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in water (10 mL)
  6. addition1N hydrochloric acid (2.00 mL) was added at 0° C
  7. filtrationThe resulting precipitate was collected by filtration
  8. customto give the title object compound (415 mg, 37%, 99.9% ee) as a white solid

Sources & evidence

ORD record
ord-405901910a9d4f5fac86316f16dad24a
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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