2-Amino-4-phenylphenol → 2-[5-Methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-5-phenyl-1,3-benzoxazole

HRID 2400574Notes

Reaction equation

HRID 2400574 reaction equation
[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=2)[N:5]=[C:4]([C:15]([OH:17])=O)[CH:3]=1.[NH2:18][C:19]1[CH:20]=[C:21]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:22]=[CH:23][C:24]=1O.C[Si](OP(=O)=O)(C)C>>[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[CH:9]=[CH:10][C:11]([CH3:14])=[CH:12][CH:13]=2)[N:5]=[C:4]([C:15]2[O:17][C:24]3[CH:23]=[CH:22][C:21]([C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=4)=[CH:20][C:19]=3[N:18]=2)[CH:3]=1

Participants

4

Reactant 3

HCID 145622-Amino-4-phenylphenolHCID 27470481-(4-Methylbenzyl)-5-methyl-1H-pyrazole-3-carboxylic acid2×HCID 16133246Trimethyl(phosphooxy)silane

Product 1

HCID 251186952-[5-Methyl-1-(4-methylbenzyl)-1H-pyrazol-3-yl]-5-phenyl-1,3-benzoxazoleYield 27%

Conditions

Temperature
180 °C

Procedure

A flask containing 5-methyl-1-(4-methylbenzyl)-1H-pyrazole-3-carboxylic acid (Intermediate B, 5.0 g, 21.7 mmol), 3-aminobiphenyl-4-ol (4.0 g, 21.7 mmol) and trimethylsilyl polyphosphate (40 g) was heated at 180° C. for 30 min, and then the reaction mixture was poured into ice water (1 L). The mixture was stirred for 1 h and was extracted with dichloromethane (2 L). The layers were separated and the organic layer was washed with brine (2×1 L) and dried with sodium sulfate. The solvent was evaporated, and the residue was purified with an ISCO CombiFlash Companion using gradient elution from 100% hexane to 20% ethyl acetate in hexane to afford the title compound as a white solid (2.19 g, 27%): 1H NMR (300 MHz, CD2Cl2) 7.94 (d, 1H), 7.66 (m, 4H), 7.48 (t, 2H), 7.39 (m, 1H), 7.14 (dd, 4H), 6.82 (s, 1H), 5.37 (s, 2H), 2.34 (s, 3H), 2.32 (s, 3H); ES-MS m/z 380.2 (MH)+, HPLC RT (Method A) 4.25 min.

Workup

  1. extractionwas extracted with dichloromethane (2 L)
  2. customThe layers were separated
  3. washthe organic layer was washed with brine (2×1 L)
  4. dry with materialdried with sodium sulfate
  5. customThe solvent was evaporated
  6. customthe residue was purified with an ISCO CombiFlash Companion
  7. washelution from 100% hexane to 20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-fdf09fd313104cab87846cf71ae7b244
Source dataset
uspto-grants-2014_08
Patent number
US08796253B2

Reaction notes

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