Sodium Hydroxide → HCID 70279186, compound

HRID 1655104Notes

Reaction equation

HRID 1655104 reaction equation
[Li+].CCC[CH2-].[CH3:6][C:7](=[N:9][OH:10])[CH3:8].CO[C:13](=[O:32])[C@@H:14]1[CH2:18][C@@H:17]([O:19][C:20](=[O:30])[C:21]2C(C)=CC(C)=CC=2C)[CH2:16][N:15]1[CH3:31].[OH-:33].[Na+]>C1COCC1.O>[C:20]([OH:19])(=[O:30])[C:21]([OH:10])=[O:33].[CH3:8][C:7]1[CH:6]=[C:13]([C@H:14]2[CH2:18][C@H:17]([OH:19])[CH2:16][N:15]2[CH3:31])[O:32][N:9]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 61028n-Butyl lithiumHCID 67180Acetone, oximeHCID 53821873HCID 53821873, compound

Product 1

HCID 70279186HCID 70279186, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

N-butyllithium (1.70 mL, 2.5 M, 4.26 mmol) was added dropwise at 0° C. to a solution of acetone oxime (155.5 mg, 2.13 mmol)in anhydrous THF (10.0 mL). The resulting solution was stirred at the same temperature for two hours. trans-1-Methyl-4-(2,4,6-trimethylbenzoyloxy) proline methyl ester (21c, 500.0 mg, 1.64 mmol)in anhydrous THF (5.0 mL) was slowly added to the solution through syringe. The resulting mixture was further stirred at 0 ° C for eight hours and slowly warmed to room temperature overnight. THF was then evaporated in vacuo. A THF-sulfuric acid solution (10.0 mL, prepared in a ratio of sulfuric acid: THF: H2O=8.2 g: 40 mL: 10 mL) was added and the mixture was refluxed for two hours. The mixture was made basic with 10% NaOH and extracted with ethyl acetate (30 mL 4X). The combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The resulting residue was purified by flash chromatography on silica gel eluting with ethyl acetate/hexane (1:1 and 2:1) to give 112.5 mg (21% yield) of the title compound (21 d) as an oil. TLC Rf =0.63 (ethyl acetate:hexane=2:l ). MS (DCl/NH3) m/e 329 (M+H)+. 1H NMR (CDCl3) δ: 6.86 (s, 2H, 2ArH), 6.03 (s, 1 H, isoxazole H), 5.48-5.54 (m, 1 H, OCH), 3.76 (dd, J =9.6, J=6.3 Hz, 1H, ArCHN), 2.38-2.61 (m, 4H, 2CH2), 2.44 (s, 3H, NCH3), 2.31 (s, 6H, 2ARCH3), 2.30 (s, isoxazole-CH3), 2.29 (s, 3H, ARCH3).

Workup

  1. stirringThe resulting mixture was further stirred at 0 ° C for eight hours
  2. customTHF was then evaporated in vacuo
  3. customA THF-sulfuric acid solution (10.0 mL, prepared in a ratio of sulfuric acid
  4. temperaturethe mixture was refluxed for two hours
  5. extractionextracted with ethyl acetate (30 mL 4X)
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe resulting residue was purified by flash chromatography on silica gel eluting with ethyl acetate/hexane (1:1 and 2:1)

Sources & evidence

ORD record
ord-63a71ab3a00e4ffd803898c4e517572d
Source dataset
uspto-grants-1995_04
Patent number
US05409946

Reaction notes

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