Methyl Glycolate → HCID 16005275, compound

HRID 348497Notes

Reaction equation

HRID 348497 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[C:12]([N:19]3[CH2:24][CH2:23][C:22]([C:26]4[CH:31]=[CH:30][C:29]([Br:32])=[CH:28][CH:27]=4)([OH:25])[CH2:21][CH2:20]3)=[N:13][C:14](SC)=[N:15][CH:16]=2)=[O:10])=[CH:4][CH:3]=1.C1C=C(Cl)C=C(C(OO)=O)C=1.C1CCN2C(=NCCC2)CC1.[C:55]([O:59][CH3:60])(=[O:58])[CH2:56][OH:57]>CC(C)=O.C1COCC1.O>[CH3:60][O:59][C:55](=[O:58])[CH2:56][O:57][C:14]1[N:13]=[C:12]([N:19]2[CH2:24][CH2:23][C:22]([C:26]3[CH:31]=[CH:30][C:29]([Br:32])=[CH:28][CH:27]=3)([OH:25])[CH2:21][CH2:20]2)[C:11]([C:9](=[O:10])[NH:8][C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)=[CH:16][N:15]=1

Participants

8

Reactant 4

HCID 66774Methyl GlycolateHCID 70297m-Chloroperbenzoic acidHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 16005274HCID 16005274, compound

Product 1

HCID 16005275HCID 16005275, compound

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-[4-(4-bromophenyl)-4-hydroxy-piperidin-1-yl]-2-methylsulfanylpyrimidine-5-carboxylic acid (4-fluorophenyl)amide (700 mg, 1.35 mmol) in acetone (50 mL) was added m-CPBA (330 mg, 1.49 mmol) and the mixture was stirred for 12 h. The mixture was concentrated under reduced pressure and the intermediate product was isolated by trituration from a mixture of hexanes and dichloromethane (1:1, 25mL). This afforded 534 mg of the intermediate product as a mixture of sulfoxide and sulfone. Said intermediate product was used hereinafter without further purification. To a solution of the sulfone/sulfoxide mixture (150 mg, 0.28 mmol) in THF (10 mL) was added DBU (200 mL) followed by methyl glycolate (50 mg, 0.56 mmol). The mixture was heated at reflux for 12 h. The mixture was poured into water and extracted with ethyl acetate (3×25 mL). The combined extracts were washed with water and brine and were dried over magnesium sulfate. Filtration and concentration afforded a white solid which was purified via recrystallization from hexane and dichloromethane (10:1). The afforded 125 mg of the titled product.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customthe intermediate product was isolated by trituration from a mixture of hexanes and dichloromethane (1:1, 25mL)
  3. customwas used hereinafter without further purification
  4. temperatureThe mixture was heated
  5. temperatureat reflux for 12 h
  6. extractionextracted with ethyl acetate (3×25 mL)
  7. washThe combined extracts were washed with water and brine
  8. dry with materialwere dried over magnesium sulfate
  9. filtrationFiltration and concentration
  10. customafforded a white solid which
  11. customwas purified via recrystallization from hexane and dichloromethane (10:1)

Sources & evidence

ORD record
ord-01639ebf0f6a40f7966983830d3c5bf3
Source dataset
uspto-grants-2007_02
Patent number
US07176310B1

Reaction notes

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