Lithium Hydroxide → HCID 44227312, compound

HRID 2091031Notes

Reaction equation

HRID 2091031 reaction equation
[CH:1]1([CH:7]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]([N:27]([CH3:35])[CH2:28][CH2:29][C:30]([O:32]CC)=[O:31])=[O:26])=[CH:21][CH:20]=2)[C:8]2[O: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.C(O)C.[OH-].[Li+]>C(O)C.O1CCCC1>[CH:1]1([CH:7]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]([N:27]([CH3:35])[CH2:28][CH2:29][C:30]([OH:32])=[O:31])=[O:26])=[CH:21][CH:20]=2)[C:8]2[O: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 3

HCID 3939Lithium HydroxideHCID 21879635Ethanol hexaneHCID 66778390HCID 66778390, compound

Product 1

HCID 44227312HCID 44227312, compoundYield 0.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

Ethyl 3-{[(4-{[cyclohexyl(3-methyl-1-benzofuran-2-yl)methyl]amino}phenyl)carbonyl](methyl)amino}propanoate (9.85 g) synthesized in Example A16 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 (4.85 g, 99.9% ee). To a mixture of the obtained amorphous form, ethanol (20 mL) and tetrahydrofuran (20 mL) was added 1N lithium hydroxide (22 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 (4.41 g, 97%, 99.9% ee) as a white solid. The obtained white solid (50 mg) was crystallized from ethanol/water to give ethanol-containing crystals (41 mg). The ethanol-containing crystals (35 mg) were recrystallized from diethyl ether to give colorless crystal (18 mg) free of solvent.

Workup

  1. additionThe fraction containing an optically active form
  2. concentrationwas concentrated
  3. customto give an amorphous form (4.85 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 (4.41 g, 97%, 99.9% ee) as a white solid
  9. customThe obtained white solid (50 mg) was crystallized from ethanol/water
  10. customto give ethanol-
  11. customwere recrystallized from diethyl ether

Sources & evidence

ORD record
ord-6d42cf5dea964c168a1c585d5deea909
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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