Cesium carbonate → tert-butyl (R)-1-(4-amino-2-(1-methyl-1H-pyrazol-5-yl)phenoxy)propan-2-ylcarbamate

HRID 1425533Notes

Reaction equation

HRID 1425533 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][C@H:17]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH3:18].C(=O)([O-])[O-].[Cs+].[Cs+]>CC(C)=O>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:18][C@H:17]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:23])([CH3:25])[CH3:24])[CH3:16])=[C:4]([C:9]2[N:13]([CH3:14])[N:12]=[CH:11][CH:10]=2)[CH:3]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 57081792(R)-tert-butyl 1-bromopropan-2-ylcarbamateHCID 1355820244-amino-2-(1-methyl-1H-pyrazol-5-yl)phenol

Product 1

HCID 86633179tert-butyl (R)-1-(4-amino-2-(1-methyl-1H-pyrazol-5-yl)phenoxy)propan-2-ylcarbamateYield 53.3%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
100 °C

Procedure

4-amino-2-(1-methyl-1H-pyrazol-5-yl)phenol (500 mg, 2643 μmol), (R)-tert-butyl 1-bromopropan-2-ylcarbamate (755 mg, 3171 μmol) and cesium carbonate (1205 mg, 3700 μmol) were weighed into a vial with anhydrous acetone (3.0 mL). The reaction was heated in a microwave at 100° C. for an hour. After this time, the crude LC/MS showed that the reaction was nearly complete. Thus, the solvent was evaporated and the resulting material was extracted (3 mL each of H2O and CH2Cl2). The aqueous layer was extracted again with CH2Cl2 (3 mL). The combined organic layer was dried over MgSO4, filtered, and concentrated. The product was purified by column chromatography (0, 20, 50, 70, 100% EtOAc/Hexanes) to yield tert-butyl (R)-1-(4-amino-2-(1-methyl-1H-pyrazol-5-yl)phenoxy)propan-2-ylcarbamate (487 mg, 1.41 mmol, 50.7%) as a light brown colored oil. LCMS m/z 347.1 (M+H); 1H NMR (400 MHz, MeOH-d4) δ ppm 0.92 (d, J=6.57 Hz, 3 H), 1.32 (s, 9 H), 3.60 (s, 3 H), 3.69-3.76 (m, 1 H), 3.79-3.94 (m, 2 H), 6.13 (d, J=1.77 Hz, 1 H), 6.57 (d, J=2.78 Hz, 1 H), 6.72 (dd, J=8.59, 2.78 Hz, 1 H), 6.83 (d, J=8.84 Hz, 1 H), 7.36 (d, J=2.02 Hz, 1 H).

Workup

  1. customThus, the solvent was evaporated
  2. extractionthe resulting material was extracted (3 mL each of H2O and CH2Cl2)
  3. extractionThe aqueous layer was extracted again with CH2Cl2 (3 mL)
  4. dry with materialThe combined organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe product was purified by column chromatography (0, 20, 50, 70, 100% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-c3d5668c3569414fb8a9398c14a871fb
Source dataset
uspto-grants-2015_01
Patent number
USRE045336E1

Reaction notes

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