Di-tert-butyl azodicarboxylate → Di-tert-butyl 1-{3-[(4,4-difluoropiperidin-1-yl)methyl]phenyl}hydrazine-1,2-dicarboxylate

HRID 572075Notes

Reaction equation

HRID 572075 reaction equation
C([Li])CCC.Br[C:7]1[CH:8]=[C:9]([CH:19]=[CH:20][CH:21]=1)[CH2:10][N:11]1[CH2:16][CH2:15][C:14]([F:18])([F:17])[CH2:13][CH2:12]1.[N:22]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])=[N:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25]>C1COCC1>[F:17][C:14]1([F:18])[CH2:15][CH2:16][N:11]([CH2:10][C:9]2[CH:8]=[C:7]([N:22]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[NH:23][C:24]([O:26][C:27]([CH3:28])([CH3:29])[CH3:30])=[O:25])[CH:21]=[CH:20][CH:19]=2)[CH2:12][CH2:13]1

Participants

5

Reactant 3

HCID 97268Di-tert-butyl azodicarboxylateHCID 866866881-[(3-Bromophenyl)methyl]-4,4-difluoropiperidineHCID 178418339Butyllithium

Product 1

HCID 86686689Di-tert-butyl 1-{3-[(4,4-difluoropiperidin-1-yl)methyl]phenyl}hydrazine-1,2-dicarboxylateYield 43.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

n-Butyllithium (1.6 M in hexanes, 4.5 mL, 7.28 mmol) was added dropwise to a stirred solution of Intermediate 12a (1.98 g, 6.82 mmol) in dry THF (15 mL) at −78° C. under nitrogen. The mixture was stirred at −78° C. for 10 min, then di-tert-butyl azodicarboxylate (1.73 g, 7.51 mmol) was added in one portion. The mixture was stirred at −78° C. for 20 min, then allowed to warm to RT over 20 min. The mixture was then partitioned between saturated ammonium chloride solution (15 mL) and ethyl acetate (3×20 mL). The combined organic extracts were washed with brine (20 mL) and dried (Na2SO4). The solvent was evaporated and the residue purified by FCC, eluting with 0-100% EtOAc in pentane, to give the title compound as a pale yellow oil (1.30 g, 43%). LCMS (Method 1): Rt 2.54 min, m/z 442 [MH+].

Workup

  1. stirringThe mixture was stirred at −78° C. for 20 min
  2. temperatureto warm to RT over 20 min
  3. customThe mixture was then partitioned between saturated ammonium chloride solution (15 mL) and ethyl acetate (3×20 mL)
  4. washThe combined organic extracts were washed with brine (20 mL)
  5. dry with materialdried (Na2SO4)
  6. customThe solvent was evaporated
  7. customthe residue purified by FCC
  8. washeluting with 0-100% EtOAc in pentane

Sources & evidence

ORD record
ord-d5c37a94dee74a31a8211dddb17e72ce
Source dataset
uspto-grants-2015_05
Patent number
US09029373B2

Reaction notes

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