Sodium Hydroxide → {5-tert-Butyl-2-[3-(2-hydroxy-ethoxy)-phenyl]-2H-pyrazol-3-yl}-carbamic acid 2,2,2-trichloro-ethyl ester

HRID 631010Notes

Reaction equation

HRID 631010 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:8]=[C:9]([CH:14]=[CH:15][CH:16]=2)[O:10][CH2:11][CH2:12][OH:13])[N:5]=[C:4]([C:17]([CH3:20])([CH3:19])[CH3:18])[CH:3]=1.[OH-].[Na+].Cl[C:24]([O:26][CH2:27][C:28]([Cl:31])([Cl:30])[Cl:29])=[O:25]>CCOC(C)=O>[Cl:29][C:28]([Cl:31])([Cl:30])[CH2:27][O:26][C:24](=[O:25])[NH:1][C:2]1[N:6]([C:7]2[CH:16]=[CH:15][CH:14]=[C:9]([O:10][CH2:11][CH2:12][OH:13])[CH:8]=2)[N:5]=[C:4]([C:17]([CH3:20])([CH3:19])[CH3:18])[CH:3]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 870632,2,2-Trichloroethyl chloroformateHCID 591518232-[3-(5-Amino-3-tert-butyl-pyrazol-1-yl)-phenoxy]-ethanol

Product 1

HCID 59151941{5-tert-Butyl-2-[3-(2-hydroxy-ethoxy)-phenyl]-2H-pyrazol-3-yl}-carbamic acid 2,2,2-trichloro-ethyl esterYield 58%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A solution of Intermediate 186a (1.0 g, 3.63 mmol) in EtOAc (20 mL) was treated with aqueous NaOH (1M, 6.53 mmol), followed by 2,2,2-trichloroethyl chloroformate (0.529 mL, 3.85 mmol) and the reaction mixture was stirred at RT for 1 h. The mixture was partitioned between EtOAc (20 mL) and water (20 mL). The layers were separated and the aqueous layer was extracted with a further 20 mL EtOAc. The combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by FCC, using 0-40% EtOAc in DCM. The combined fractions were evaporated under reduced pressure and the product was triturated with DCM. The solid was filtered and washed with Diethyl ether to afford the title compound as a white solid (0.930 g, 58%). LCMS (Method 3): Rt 4.01 min, m/z 450 [M].

Workup

  1. customThe mixture was partitioned between EtOAc (20 mL) and water (20 mL)
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with a further 20 mL EtOAc
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by FCC
  8. customThe combined fractions were evaporated under reduced pressure
  9. customthe product was triturated with DCM
  10. filtrationThe solid was filtered
  11. washwashed with Diethyl ether

Sources & evidence

ORD record
ord-9681d527fc7349519ca6fb20362cbcda
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Reaction notes

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