Sodium Carbonate → HCID 69230925, compound

HRID 1181062Notes

Reaction equation

HRID 1181062 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].[N:40]1[CH:45]=[CH:44][CH:43]=[C:42](B(O)O)[CH:41]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)CC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[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]([C:42]4[CH:41]=[N:40][CH:45]=[CH:44][CH:43]=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 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 27343783-Pyridinylboronic acidHCID 58979029HCID 58979029, compound

Product 1

HCID 69230925HCID 69230925, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 10311-PropanolSolvent

Procedure

Suzuki Coupling Using Aryl Boronic Acids: 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 (450 mg, 0.75 mmol), 3-pyridineboronic acid (120 mg, 0.97 mmol), triphenylphosphine (6 mg, 0.024 mmol), 2M aqueous sodium carbonate (3 mL) in n-propanol (15 mL) was sparged with nitrogen for 5 min. Palladium acetate (2 mg, 0.008 mmol) was added, and the reaction was heated to reflux under a blanket of nitrogen for 4 h. The reaction mixture was concentrated and then partitioned between water/EtOAc. The organic layer was dried (MgSO4) and concentrated to crude product (290 mg). This material was purified by silica gel column chromatography to yield 3-(2-(isopropoxycarbonylamino-methyl)-4-{2-[5-methyl-2-(4-pyridin-3-yl-phenyl)-oxazol-4-yl]-ethoxy}-phenyl)-propionic acid tert-butyl ester was obtained as a white solid (230 mg, 51%). 1H NMR (CDCl3) δ1.25 (d, 6H), 1.42 (s, 9H), 2.42 (s, 3H), 2.51 (t, 2H), 2.89 (t, 2H), 3.05 (t, 2H), 4.26 (t, 2H), 4.36 (d, 2H), 4.96 (m, 2H), 6.78 (dd, 1H), 6.87 (d, 1H), 7.21 (d, 1H), 7.47 (dd, 1H), 7.67 (d, 2H), 8.00 (dt, 1H), 8.12 (d, 2H), 8.65 (dd, 1H), 8.94 (s, 1H). MS [EI+] m/z 600 (M+H).

Workup

  1. customwas sparged with nitrogen for 5 min
  2. temperaturethe reaction was heated
  3. temperatureto reflux under a blanket of nitrogen for 4 h
  4. concentrationThe reaction mixture was concentrated
  5. custompartitioned between water/EtOAc
  6. dry with materialThe organic layer was dried (MgSO4)
  7. concentrationconcentrated to crude product (290 mg)
  8. customThis material was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-a8182b27f15146a790e227ddee41a374
Source dataset
uspto-grants-2007_10
Patent number
US07282501B2

Reaction notes

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