Sodium Hydroxide → HCID 18794804, compound

HRID 400126Notes

Reaction equation

HRID 400126 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[N:10]([CH2:12][CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][CH:22]([O:27][CH3:28])[C:23]([O:25]C)=[O:24])=[CH:17][CH:16]=1)[CH3:11].[OH-].[Na+]>O.CC(C)=O>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[N:10]([CH2:12][CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][CH:22]([O:27][CH3:28])[C:23]([OH:25])=[O:24])=[CH:17][CH:16]=1)[CH3:11]

Participants

5

Reactant 2

HCID 14798Sodium Hydroxide2×HCID 22713083HCID 22713083, compound

Product 1

HCID 18794804HCID 18794804, compoundYield 73.7%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

Lipase from Rhizopus delemar (300 mg, ex. Biocatalysts Ltd.) was stirred in deionised water (125 ml) and the pH of the mixture adjusted to 7.0. To this mixture, at ambient temperature (23° C.), was added a solution of methyl 3-[4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]phenyl]-2-methoxypropanoate (690 mg) (enantiomer ratio 8:92 as prepared in example 1) in acetone (5 ml). The resulting reaction mixture was stirred at ambient temperature and pH 7.0 was maintained by autotitration with 0.1M sodium hydroxide solution until hydrolysis was complete. 0.1M Sodium hydroxide solution was added to bring the reaction mixture to pH 9.5 after which it was washed with dichloromethane. The aqueous phase was acidified with hydrochloric acid to pH1 and the acid extracted into dichloromethane, washed, dried (magnesium sulphate), and evaporated. The resulting solid was triturated with hexane to yield 490 mg of (+)3-[4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]phenyl]-2-methoxypropanoic acid as a white solid; m.p. 121°-123° C.; enantiomer ratio 92.8 (by HPLC assay); [a]D25 +13°, MeOH, c 0.5. Enantiomer ratios of 3-[4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]phenyl]-2-methoxypropanoic acid were determined by HPLC on a chiral AGP column eluting with 4.8% acetonitrile in 0.01M sodium dihyrogen phosphate solution at pH 7.0 and detecting products by UV monitoring at 245 nm. Enantiomer ratios are quoted in the order of elution.

Workup

  1. customThe resulting reaction mixture
  2. washwas washed with dichloromethane
  3. extractionthe acid extracted into dichloromethane
  4. washwashed
  5. dry with materialdried (magnesium sulphate)
  6. customevaporated
  7. customThe resulting solid was triturated with hexane

Sources & evidence

ORD record
ord-0eec9b3ff8ac4f40be89d1aa0b069bd7
Source dataset
uspto-grants-1998_10
Patent number
US05827865

Reaction notes

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