Potassium Carbonate → tert-butyl 2-(4-amino-2-(1-methyl-1H-pyrazol-5-yl)phenoxy)ethylcarbamate

HRID 521607Notes

Reaction equation

HRID 521607 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([C:9]2[N:13]([CH3:14])[N:12]=[CH:11][CH:10]=2)[CH:3]=1.Br[CH2:16][CH2:17][NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:16][CH2:17][NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[C:4]([C:9]2[N:13]([CH3:14])[N:12]=[CH:11][CH:10]=2)[CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 4103526tert-Butyl N-(2-bromoethyl)carbamateHCID 1355820244-amino-2-(1-methyl-1H-pyrazol-5-yl)phenol

Product 1

HCID 67265127tert-butyl 2-(4-amino-2-(1-methyl-1H-pyrazol-5-yl)phenoxy)ethylcarbamateYield 44.4%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
60 °C

Procedure

4-amino-2-(1-methyl-1H-pyrazol-5-yl)phenol (2 g, 10.6 mmol) was dissolved in acetone (100 mL). Tert-butyl 2-bromoethylcarbamate (4.74 g, 21.2 mmol) and potassium carbonate (2.92 g, 21.2 mmol) were then added to the solution. The reaction was refluxed for 15 hours at 60° C. After the reaction was completed, the reaction mixture was filtered, concentrated, and dissolved in CH2Cl2. The unreacted 4-amino-2-(1-methyl-1H-pyrazol-5-yl)phenol was removed from the product through extraction with 1N NaOH. The product was purified by column chromatography (40% EtOAc/60% Hexanes) to yield tert-butyl 2-(4-amino-2-(1-methyl-1H-pyrazol-5-yl)phenoxy)ethylcarbamate (1.56 g, 4.70 mmol, 44.4%) as a white solid. LCMS m/z (%)=333 (M+H). 1H NMR (400 MHz, CDCl3) δ ppm 1.42 (s, 9H), 3.33 (q, J=5.31 Hz, 2H), 3.55 (s, 2H), 3.74 (s, 3H), 3.90 (t, J=5.05 Hz, 2H), 4.63 (br. s., 1H), 6.22 (d, J=1.77 Hz, 1H), 6.61 (d, J=3.03 Hz, 1H), 6.73 (dd, J=8.84, 2.78 Hz, 1H), 6.84 (d, J=8.84 Hz, 1H), 7.51 (d, J=1.77 Hz, 1H).

Workup

  1. filtrationthe reaction mixture was filtered
  2. concentrationconcentrated
  3. dissolutiondissolved in CH2Cl2
  4. customThe unreacted 4-amino-2-(1-methyl-1H-pyrazol-5-yl)phenol was removed from the product through extraction with 1N NaOH
  5. customThe product was purified by column chromatography (40% EtOAc/60% Hexanes)

Sources & evidence

ORD record
ord-a2bf1f19cc1745cc9a1aed19fa4f6471
Source dataset
uspto-grants-2016_05
Patent number
US09328107B2

Reaction notes

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