Diisopropylamine → HCID 10991586, compound

HRID 1418051Notes

Reaction equation

HRID 1418051 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[Si:13]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].[F:28][C:29]1[CH:40]=[CH:39][C:32]([C:33](N(OC)C)=[O:34])=[CH:31][CH:30]=1.[Cl-].[NH4+]>C1COCC1.O>[F:28][C:29]1[CH:40]=[CH:39][C:32]([C:33]([CH:21]([C:22]2[CH:23]=[CH:24][N:25]=[CH:26][CH:27]=2)[O:20][Si:13]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14])=[O:34])=[CH:31][CH:30]=1

Participants

8

Reactant 5

HCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 109878804-(Tert-butyldimethylsilyloxymethyl)pyridineHCID 140693474-Fluoro-N-methoxy-N-methylbenzamideHCID 178418339Butyllithium

Product 1

HCID 10991586HCID 10991586, compoundYield 79.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

Into a 2 L 3-necked round bottom flask fitted with a thermometer, dry nitrogen gas inlet, addition funnel and mechanical stirrer was added diisopropylamine (65 mL, 0.46 mol) in THF (120 mL). Cooled to -20° C. with a isopropyl alcohol/dry ice bath and added a solution of n-butyllithium in hexanes (210 mL of a 2.5M solution, 0.53 mol). Stirred at -15° C. for 30 min, then cooled to -20° C. Added 4-t-butydimethylsilyloxymethylpyridine from Step A (98.2 g, 0.44 mol) neat over a 30 min period. Let stir for 45 min at -20° C. To this mixture was added a solution of 4-fluoro-N-methoxy-N-methyl-benzamide (84.5 g, 0.46 mol) in THF (90 mL) over a 30 min period. The dark solution was stirred at 0° C. for 1 h, then warmed slowly to room temperature for 30 min. The reaction was poured into water (500 mL) containing ammonium chloride (100 g). After stirring for 10 min at room temperature, the solution was extracted with ethyl acetate (3 times). The combined organic extracts were washed successively with water and saturated salt solution. The combined aqueous layers were extracted with ethyl acetate. The combined ethyl acetate extracts were dried over anhydrous magnesium sulfate. The solution was filtered and the solvent removed by rotoevaporation. The residue was purified by flash column chromatography on silica gel eluted with 15-50% ethyl acetate in hexanes (17 L in total). The solvent was removed by rotoevaporation to yield the tide compound as an amber oil (120.4 g, 74% yield).

Workup

  1. customInto a 2 L 3-necked round bottom flask fitted with a thermometer, dry nitrogen gas inlet, addition funnel and mechanical stirrer
  2. temperaturecooled to -20° C
  3. stirringLet stir for 45 min at -20° C
  4. stirringThe dark solution was stirred at 0° C. for 1 h
  5. temperaturewarmed slowly to room temperature for 30 min
  6. stirringAfter stirring for 10 min at room temperature
  7. extractionthe solution was extracted with ethyl acetate (3 times)
  8. washThe combined organic extracts were washed successively with water and saturated salt solution
  9. extractionThe combined aqueous layers were extracted with ethyl acetate
  10. dry with materialThe combined ethyl acetate extracts were dried over anhydrous magnesium sulfate
  11. filtrationThe solution was filtered
  12. customthe solvent removed by rotoevaporation
  13. customThe residue was purified by flash column chromatography on silica gel
  14. washeluted with 15-50% ethyl acetate in hexanes (17 L in total)
  15. customThe solvent was removed by rotoevaporation

Sources & evidence

ORD record
ord-68adca22c7144c3492ceb7f99812c161
Source dataset
uspto-grants-1999_03
Patent number
US05880139

Reaction notes

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