Hydroxyacetone → (R)-3-hydroxy-5-methoxy-6-methyl-2-[2-(3-methyl-1,2,4-oxadiazol-5-yl)-2-(4-methyl-oxazol-2-ylamino)-ethylsulfanylmethyl]-benzoic acid methyl ester

HRID 234244Notes

Reaction equation

HRID 234244 reaction equation
[CH3:1][O:2][C:3](=[O:36])[C:4]1[C:9]([CH3:10])=[C:8]([O:11][CH3:12])[CH:7]=[C:6]([O:13][Si](C)(C)C(C)(C)C(C)C)[C:5]=1[CH2:23][S:24][CH2:25][C@H:26]([NH:33][C:34]#[N:35])[C:27]1[O:31][N:30]=[C:29]([CH3:32])[N:28]=1.[OH:37][CH2:38][C:39](=O)[CH3:40]>O1CCCC1.[OH-].[Na+].O>[CH3:1][O:2][C:3](=[O:36])[C:4]1[C:9]([CH3:10])=[C:8]([O:11][CH3:12])[CH:7]=[C:6]([OH:13])[C:5]=1[CH2:23][S:24][CH2:25][C@@H:26]([C:27]1[O:31][N:30]=[C:29]([CH3:32])[N:28]=1)[NH:33][C:34]1[O:37][CH:38]=[C:39]([CH3:40])[N:35]=1

Participants

6

Reactant 2

HCID 8299HydroxyacetoneHCID 53958922HCID 53958922, compound

Product 1

HCID 53762937(R)-3-hydroxy-5-methoxy-6-methyl-2-[2-(3-methyl-1,2,4-oxadiazol-5-yl)-2-(4-methyl-oxazol-2-ylamino)-ethylsulfanylmethyl]-benzoic acid methyl ester

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
40 °C

Procedure

To a stirred solution of 260 mg of (R)-3-[dimethyl-(1,1,2-trimethyl-propyl)-silanyloxy]-2-[2-cyanoamino-2-(3-methyl-1,2,4-oxadiazol-5-yl)-ethylsulfanylmethyl]-5-methoxy-6-methyl-benzoic acid methyl ester in 50 ml of tetrahydrofuran were added 0.1 ml of 25% aqueous hydroxyacetone and 0.09 ml of IN sodium hydroxide solution. The suspension was stirred for 12 h at 40° C. After cooling, the mixture was diluted with 100 ml water and subsequently extracted with 200 ml ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and evaporated in vacuo. The residue was chromatographed on silica gel using ethyl acetate/hexane (1:1, v/v) as eluent, and the purified product was treated with ammonium fluoride in methanol in an analogous manner to the procedure described in Example 1 to yield (R)-3-hydroxy-5-methoxy-6-methyl-2-[2-(3-methyl-1,2,4-oxadiazol-5-yl)-2-(4-methyl-oxazol-2-ylamino)-ethylsulfanylmethyl]-benzoic acid methyl ester as a white powder.

Workup

  1. temperatureAfter cooling
  2. extractionsubsequently extracted with 200 ml ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated in vacuo
  6. customThe residue was chromatographed on silica gel
  7. additionv/v) as eluent, and the purified product was treated with ammonium fluoride in methanol in an analogous manner to the procedure

Sources & evidence

ORD record
ord-a633276c06fc4c00988a5def4b3ad5a4
Source dataset
uspto-grants-1997_01
Patent number
US05594135

Reaction notes

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