Phenol → HCID 69231925, compound

HRID 1181065Notes

Reaction equation

HRID 1181065 reaction equation
[C:1]([O:5][C:6](=[O:39])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][C:18]2[N:19]=[C:20]([C:24]3[CH:29]=[CH:28][C:27](Br)=[CH:26][CH:25]=3)[O:21][C:22]=2[CH3:23])=[CH:11][C:10]=1[CH2:31][NH:32][C:33]([O:35][CH:36]([CH3:38])[CH3:37])=[O:34])([CH3:4])([CH3:3])[CH3:2].[C:40]1([OH:46])[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:1]([O:5][C:6](=[O:39])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][C:18]2[N:19]=[C:20]([C:24]3[CH:29]=[CH:28][C:27]([O:46][C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=4)=[CH:26][CH:25]=3)[O:21][C:22]=2[CH3:23])=[CH:11][C:10]=1[CH2:31][NH:32][C:33]([O:35][CH:36]([CH3:38])[CH3:37])=[O:34])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 996PhenolHCID 62657Potassium Phosphate, TribasicHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 58979029HCID 58979029, compound

Product 1

HCID 69231925HCID 69231925, compoundYield 40.7%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 3-[4-{2-[2-(4-bromo-phenyl)-5-methyl-oxazol-4-yl]-ethoxy}-2-(isopropoxycarbonylamino-methyl)-phenyl]-propionic acid tert-butyl ester (0.44 mmol, 0.24 g), phenol (0.53 mmol, 0.050 g), K3PO4 (0.88 mmol, 0.19 g), 2-(di-t-butylphosphino)biphenyl (0.066 mmol, 0.020 g), and Pd(OAc)2 (0.044 mmol, 0.010 g) in toluene (7 mL) was degassed under vacuum and backfilled with nitrogen (3×) and heated at 110° C. for 18 h. Additional Pd(OAc)2 (10 mg) and 2-(di-t-butylphosphino)biphenyl (20 mg) were added to ensure complete reaction, and the mixture was heated 5 h. Upon cooling, the mixture was placed directly onto a silica gel column and eluted with 30%-50% EtOAc/hexanes to give 3-(2-(isopropoxycarbonylamino-methyl)-4-{2-[5-methyl-2-(4-phenoxy-phenyl)-oxazol-4-yl]-ethoxy}-phenyl)-propionic acid tert-butyl ester (0.11 g).

Workup

  1. customwas degassed under vacuum
  2. additionAdditional Pd(OAc)2 (10 mg) and 2-(di-t-butylphosphino)biphenyl (20 mg) were added
  3. customreaction
  4. temperaturethe mixture was heated 5 h
  5. temperatureUpon cooling
  6. washeluted with 30%-50% EtOAc/hexanes

Sources & evidence

ORD record
ord-00c48b6a50ea4765a590627dd3642ce2
Source dataset
uspto-grants-2007_10
Patent number
US07282501B2

Reaction notes

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