Diisopropylamine → HCID 59024652, compound

HRID 2054116Notes

Reaction equation

HRID 2054116 reaction equation
C([N-]C(C)C)(C)C.[Li+].[Li]CCCC.C(NC(C)C)(C)C.[CH3:21][S:22][C:23]1[CH:28]=[CH:27][C:26]([C:29](=[N:37][OH:38])[CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[CH:25][CH:24]=1.[Br:39][C:40]([F:47])([F:46])[C:41](OCC)=O>C1COCC1.Cl>[Br:39][C:40]([F:47])([F:46])[C:41]1[O:38][N:37]=[C:29]([C:26]2[CH:25]=[CH:24][C:23]([S:22][CH3:21])=[CH:28][CH:27]=2)[C:30]=1[C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1

Participants

8

Reactant 5

HCID 7912DiisopropylamineHCID 69585Ethyl bromodifluoroacetateHCID 2724682Lithium diisopropylamideHCID 73422950HCID 73422950, compoundHCID 178418339Butyllithium

Product 1

HCID 59024652HCID 59024652, compoundYield 12%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

Lithium diisopropylamide, prepared from n-BuLi (2. 5 mmol) and diisopropylamine (2.5 mmol), was added dropwise to a solution of 1-(4-methylsulfanylphenyl)-2-phenylethanone oxime (5) (257 mg, 1 mmol) in dry THF (25 mL) at −20° C. The reaction mixture was stirred at −20° C. for 1 h and then allowed to warm to room temperature for 1 h. The reaction mixture was cooled to −78° C. and ethyl bromodifluoroacetate (153 μL, 1.2 mmol) was added in one portion. After 5 h at −78° C., the reaction mixture was allowed to warm to room temperature, diluted with 1M HCl (10 mL) and extracted with CH2Cl2. The organic extracts were dried over anhydrous MgSO4, filtered and concentrated to dryness. The yellow residue was then treated with concentrated H2SO4 (25 mL) at 0° C. overnight. The reaction mixture was poured over ice-cold H2O and extracted with CH2Cl2. The organic extracts were dried over anhydrous MgSO4, filtered and concentrated. Purification by flash column chromatography with hexanes-EtOAc (4:1) yielded 6 (47 mg, 12%) as a colorless syrup: 1H NMR (CDCl3) δ 2.52 (3H, s, SMe), 7.23-7.50 (9H, m, Ar). HRMS (FAB) Calculated for C17H13BrF2NOS (MH+, 395.9865). Found: 395.9861.

Workup

  1. temperatureto warm to room temperature for 1 h
  2. temperatureThe reaction mixture was cooled to −78° C.
  3. waitAfter 5 h at −78° C.
  4. temperatureto warm to room temperature
  5. extractionextracted with CH2Cl2
  6. dry with materialThe organic extracts were dried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. additionThe yellow residue was then treated with concentrated H2SO4 (25 mL) at 0° C. overnight
  10. additionThe reaction mixture was poured over ice-cold H2O
  11. extractionextracted with CH2Cl2
  12. dry with materialThe organic extracts were dried over anhydrous MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customPurification by flash column chromatography with hexanes-EtOAc (4:1)

Sources & evidence

ORD record
ord-0e938b8bafbe432e89b2a24c9dbd854a
Source dataset
uspto-grants-2008_02
Patent number
US07329401B2

Reaction notes

Loading…