Lithium Hexamethyldisilazide → HCID 86700608, compound

HRID 929298Notes

Reaction equation

HRID 929298 reaction equation
[Cl:1][C:2]1[C:6]([NH:7][CH3:8])=[CH:5][N:4]([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)[N:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[O:25]=[C:26]1[C@H:31]2[CH2:32][C@H:28]([CH:29]=[CH:30]2)[N:27]1[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34]>C1COCC1>[C:36]([O:35][C:33](=[O:34])[NH:27][C@@H:28]1[CH2:32][C@H:31]([C:26](=[O:25])[N:7]([C:6]2[C:2]([Cl:1])=[N:3][N:4]([C:9]3[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=3)[CH:5]=2)[CH3:8])[CH:30]=[CH:29]1)([CH3:37])([CH3:38])[CH3:39]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 11830665(1R,4S)-tert-Butyl 3-oxo-2-azabicyclo[2.2.1]hept-5-ene-2-carboxylateHCID 67499849HCID 67499849, compound

Product 1

HCID 86700608HCID 86700608, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of 3-chloro-N-methyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine (0.20 g, 0.96 mmol) in THF (10 mL) was cooled to a temperature of about −78° C. LHMDS (1 M solution in hexanes, 1.0 mL, 1.00 mmol) was added, and the solution was stirred at a temperature of about −78° C. for 15 minutes. A solution of (1R,4S)-tert-butyl 3-oxo-2-azabicyclo[2.2.1]hept-5-ene-2- carboxylate (0.20 g, 0.96 mmol) dissolved in THF (3 mL) was added to the solution at a temperature of about −78° C. in one portion. After stirring for one hour at a temperature of about −78° C., the cooling bath was removed and the reaction warmed to a temperature of about 20° C. After stirring for an additional five minutes, acetic acid (AcOH, 0.1 mL) was added to the solution. The reaction mixture was concentrated and purified via silica gel chromatography eluting with EtOAc/hexanes to give the title compound F109 as a white solid (0.25 g, 59%).

Workup

  1. additionwas added to the solution at a temperature of about −78° C. in one portion
  2. stirringAfter stirring for one hour at a temperature of about −78° C.
  3. customthe cooling bath was removed
  4. temperaturethe reaction warmed to a temperature of about 20° C
  5. stirringAfter stirring for an additional five minutes
  6. additionacetic acid (AcOH, 0.1 mL) was added to the solution
  7. concentrationThe reaction mixture was concentrated
  8. custompurified via silica gel chromatography
  9. washeluting with EtOAc/hexanes

Sources & evidence

ORD record
ord-e9915baf093042bbbdd65d79489367cd
Source dataset
uspto-grants-2016_03
Patent number
US09295260B2

Reaction notes

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