Sodium Hydroxide → 4-[3-tert-Butyl-5-(2,2,2-trichloro-ethoxycarbonylamino)-pyrazol-1-yl]-piperidine-1-carboxylic acid benzyl ester

HRID 75596Notes

Reaction equation

HRID 75596 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([N:17]2[C:21]([NH2:22])=[CH:20][C:19]([C:23]([CH3:26])([CH3:25])[CH3:24])=[N:18]2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].Cl[C:30]([O:32][CH2:33][C:34]([Cl:37])([Cl:36])[Cl:35])=[O:31]>CCOC(C)=O.C1CCCCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][CH:14]([N:17]2[C:21]([NH:22][C:30]([O:32][CH2:33][C:34]([Cl:37])([Cl:36])[Cl:35])=[O:31])=[CH:20][C:19]([C:23]([CH3:26])([CH3:25])[CH3:24])=[N:18]2)[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 870632,2,2-Trichloroethyl chloroformateHCID 866866934-(5-Amino-3-tert-butyl-pyrazol-1-yl)-piperidine-1-carboxylic acid benzyl ester

Product 1

HCID 866866944-[3-tert-Butyl-5-(2,2,2-trichloro-ethoxycarbonylamino)-pyrazol-1-yl]-piperidine-1-carboxylic acid benzyl esterYield 41.1%

Reagents, catalysts & solvents 2

HCID 8078CyclohexaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of Intermediate 16b (550 mg, 1.54 mmol) in aqueous NaOH solution (1M, 3.85 mL, 3.85 mmol) and EtOAc (5 mL) at RT, was added 2,2,2-trichloroethyl chloroformate (0.32 mL, 2.31 mmol) over 2 min, then the mixture stirred vigorously for min. The aqueous layer was extracted with EtOAc (10 mL), then the combined organics washed with brine (10 mL), dried (MgSO4), filtered and concentrated in vacuo to leave a yellow-brown oil. FCC, using 0-30% EtOAc in cyclohexane, gave the title compound as a white foam (337 mg, 41%). LCMS (Method 3): Rt 4.81 min, m/z 531, 533 [MH+].

Workup

  1. extractionThe aqueous layer was extracted with EtOAc (10 mL)
  2. washthe combined organics washed with brine (10 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto leave a yellow-brown oil

Sources & evidence

ORD record
ord-e97f69901720495eb53e967465d02dfc
Source dataset
uspto-grants-2014_09
Patent number
US08835431B2

Reaction notes

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