Sodium Hydroxide → HCID 18794804, compound

HRID 362283Notes

Reaction equation

HRID 362283 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:28][CH3:29])[C:23]([O:25]CC)=[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:28][CH3:29])[C:23]([OH:25])=[O:24])=[CH:17][CH:16]=1)[CH3:11]

Participants

5

Reactant 2

HCID 14798Sodium Hydroxide2×HCID 18794789HCID 18794789, compound

Product 1

HCID 18794804HCID 18794804, compoundYield 76.4%

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); [α]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 dihydrogen 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-ff8d0223a8b94ac7b0ced0d451c91215
Source dataset
uspto-grants-1999_02
Patent number
US05869495

Reaction notes

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