Ammonium Chloride → HCID 68958100, compound

HRID 2378055Notes

Reaction equation

HRID 2378055 reaction equation
[C:1]([Si:5]([CH3:24])([CH3:23])[O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13](=[N:21][OH:22])[CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.C[O:31][C:32]([CH:34]1[CH2:36][CH2:35]1)=O.[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C>[C:1]([Si:5]([CH3:24])([CH3:23])[O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:14]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:32]([CH:34]3[CH2:36][CH2:35]3)([OH:31])[O:22][N:21]=2)=[CH:9][CH:8]=1)([CH3:2])([CH3:4])[CH3:3]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 76122Methyl cyclopropanecarboxylateHCID 72579577HCID 72579577, compoundHCID 178418339Butyllithium

Product 1

HCID 68958100HCID 68958100, compoundYield 32%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a mixture consisting of Example 1, Compound B (3.0 g) in anhydrous tetrahydrofuran (14 mL) at −5° C. under a nitrogen atmosphere is added a solution consisting of 1.6 M n-butyllithium in hexanes (12 mL.) The mixture is stirred between −5 and 0° C. for 30 minutes. To the stirring mixture at 0° C. is added a mixture consisting of cyclopropanecarboxylic acid methyl ester (1.3 g) in tetrahydrofuran (7 mL) and the resultant mixture is stirred for two hours. The mixture is raised to room temperature and is stirred for 18 hours. The mixture is then treated with saturated aqueous ammonium chloride (50 mL) and diluted with ethyl acetate (300 mL.) The organic layer is separated and is washed sequentially with an additional portion of saturated aqueous ammonium chloride (50 mL) and brine solution (50 mL.) The organic layer is separated and is dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate is purified by flash silica gel column chromatography. Elution with dichloromethane then with a mixture of hexanes-ethyl acetate (4:1 v/v) afforded the synthetic intermediate 3-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-5-cyclopropyl-4-phenyl-4,5-dihydro-isoxazol-5-ol (1.15 g.)

Workup

  1. additionis added a solution
  2. additionTo the stirring mixture at 0° C. is added a mixture
  3. stirringis stirred for 18 hours
  4. customis separated
  5. washis washed sequentially with an additional portion of saturated aqueous ammonium chloride (50 mL) and brine solution (50 mL.) The organic layer
  6. customis separated
  7. dry with materialis dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe concentrate is purified by flash silica gel column chromatography
  11. washElution with dichloromethane
  12. additionwith a mixture of hexanes-ethyl acetate (4:1 v/v)

Sources & evidence

ORD record
ord-8b59125dd8a64c39b499ca35b8ba55cd
Source dataset
uspto-grants-2008_12
Patent number
US07470715B2

Reaction notes

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