Ammonium Chloride → HCID 67815498, compound

HRID 2401352Notes

Reaction equation

HRID 2401352 reaction equation
C([O:4][CH2:5][C:6]1[C:10]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[CH:17]=[O:18])=[C:9]([CH3:19])[O:8][N:7]=1)(=O)C.[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([Mg]Br)=[CH:23][CH:22]=1.[Cl-].[NH4+].O.[OH-].[Li+]>CCOC(C)=O.C1COCC1.CO.O.O.C1COCC1>[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([CH:17]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[C:10]2[C:6]([CH2:5][OH:4])=[N:7][O:8][C:9]=2[CH3:19])[OH:18])=[CH:23][CH:22]=1

Participants

9

Reactant 4

HCID 25517Ammonium ChlorideHCID 168937Lithium hydroxide, monohydrateHCID 86666717HCID 86666717, compoundHCID 178478191HCID 178478191, compound

Product 1

HCID 67815498HCID 67815498, compoundYield 88.2%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×HCID 21892291Methanol tetrahydrofuran waterSolvent

Conditions

Temperature
-78 °C

Procedure

To a round bottomed flask was added (4-(2-formylphenyl)-5-methylisoxazol-3-yl)methyl acetate (1.01 g, 3.90 mmol) and THF (20 mL) before the reaction was cooled to −78° C. To this solution was added 1.0 M (4-chlorophenyl)magnesium bromide (4.68 mL, 4.68 mmol) and the reaction stirred at −78° C. for 30 min before addition of ammonium chloride solution. The reaction was warmed to room temperature and diluted with EtOAc. The layers were separated and the aqueous was extracted with EtOAc. The combined organics were washed with brine, dried over Na2SO4, filtered, and concentrated. The crude residue was taken up in THF:MeOH:Water (2:2:1, 20 mL) before addition of lithium hydroxide hydrate (0.491 g, 11.70 mmol). The reaction was stirred at room temperature for 1 h before diluting with water and EtOAc. The layers were separated and the aqueous was extracted with EtOAc. The combined organics were washed with brine, dried over Na2SO4, filtered, and concentrated. The crude diol was purified via Biotage (EtOAc/hex) to afford (4-chlorophenyl)(2-(3-(hydroxymethyl)-5-methylisoxazol-4-yl)phenyl)methanol (1.14 g, 3.44 mmol). LC/MS m/z 330 [M+H]+.

Workup

  1. temperatureThe reaction was warmed to room temperature
  2. customThe layers were separated
  3. extractionthe aqueous was extracted with EtOAc
  4. washThe combined organics were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe layers were separated
  9. extractionthe aqueous was extracted with EtOAc
  10. washThe combined organics were washed with brine
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe crude diol was purified via Biotage (EtOAc/hex)

Sources & evidence

ORD record
ord-8c9f8a620024479bbc732f3b481ca01c
Source dataset
uspto-grants-2014_08
Patent number
US08796261B2

Reaction notes

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