Sodium Hydroxide → HCID 66778406, compound

HRID 2091095Notes

Reaction equation

HRID 2091095 reaction equation
[CH2:1]([CH:3]([CH2:34][CH3:35])[CH:4]([NH:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]([N:25]([CH3:33])[CH2:26][CH2:27][C:28]([O:30]CC)=[O:29])=[O:24])=[CH:19][CH:18]=1)[C:5]1[O:6][C:7]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:8]=2[C:9]=1[CH3:10])[CH3:2].[OH-].[Na+]>CCCCCC.C(O)C.C(O)C.O1CCCC1>[CH2:34]([CH:3]([CH2:1][CH3:2])[CH:4]([NH:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]([N:25]([CH3:33])[CH2:26][CH2:27][C:28]([OH:30])=[O:29])=[O:24])=[CH:19][CH:18]=1)[C:5]1[O:6][C:7]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:8]=2[C:9]=1[CH3:10])[CH3:35]

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 66777633HCID 66777633, compound

Product 1

HCID 66778406HCID 66778406, compoundYield 96%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolventHCID 21879635Ethanol hexaneSolvent

Procedure

Ethyl 3-{[(4-{[2-ethyl-1-(5-fluoro-3-methyl-1-benzofuran-2-yl)butyl]amino}phenyl)carbonyl](methyl)amino}propanoate (9.18 g) obtained in Example A71(5) was dissolved in hexane-ethanol (1:1, volume ratio), subjected to HPLC using CHIRALPAK AD (50 mm ID×500 mL, manufactured by Daicel Chemical Industries, Ltd.), and eluted with hexane-ethanol (1:1, volume ratio) as a mobile phase at room temperature and at a flow rate 60 mL/min. The resulting fraction containing an optically active form having a longer retention time was concentrated to give an amorphous form (4.67 g, 99.9% ee). The obtained amorphous form (4.67 g) was dissolved in ethanol (20 mL) and tetrahydrofuran (20 mL), 1N aqueous sodium hydroxide solution (19.4 mL) was added, and the mixture was stirred at room temperature for 20 min. The solvent was evaporated under reduced pressure. Water (30 mL) was added, and the mixture was neutralized with 1N hydrochloric acid under ice-cooling and stirred for 20 min. The resulting precipitate was collected by filtration, and dried to give the title compound (4.21 g, 96%, 99.9% ee).

Workup

  1. washeluted with hexane-ethanol (1:1, volume ratio) as a mobile phase at room temperature and at a flow rate 60 mL/min
  2. additionThe resulting fraction containing an optically active form
  3. concentrationwas concentrated
  4. customto give an amorphous form (4.67 g, 99.9% ee)
  5. customThe solvent was evaporated under reduced pressure
  6. additionWater (30 mL) was added
  7. temperaturecooling
  8. stirringstirred for 20 min
  9. filtrationThe resulting precipitate was collected by filtration
  10. customdried

Sources & evidence

ORD record
ord-f25f1ea546054cbfba63fe29983e7960
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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