Sodium Carbonate → HCID 69872478, compound

HRID 398132Notes

Reaction equation

HRID 398132 reaction equation
[CH2:1]([O:3][C:4](=[O:39])[C:5]([CH3:38])([O:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][C:17]2[N:18]=[C:19]([C:23]3[CH:28]=[CH:27][C:26](B4OC(C)(C)C(C)(C)O4)=[CH:25][CH:24]=3)[O:20][C:21]=2[CH3:22])=[CH:10][CH:9]=1)[CH3:6])[CH3:2].Br[C:41]1[N:46]=[CH:45][CH:44]=[CH:43][N:42]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(O)(C)C>[CH2:1]([O:3][C:4](=[O:39])[C:5]([CH3:38])([O:7][C:8]1[CH:9]=[CH:10][C:11]([O:14][CH2:15][CH2:16][C:17]2[N:18]=[C:19]([C:23]3[CH:28]=[CH:27][C:26]([C:41]4[N:46]=[CH:45][CH:44]=[CH:43][N:42]=4)=[CH:25][CH:24]=3)[O:20][C:21]=2[CH3:22])=[CH:12][CH:13]=1)[CH3:6])[CH3:2]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 783452-BromopyrimidineHCID 23589997HCID 23589997, compound

Product 1

HCID 69872478HCID 69872478, compoundYield 28%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 3776IsopropanolSolvent

Conditions

Temperature
86 °C

Procedure

A 50 mL flask was charged with 2-methyl-2-[4-(2-{5-methyl-2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-oxazol-4-yl}-ethoxy)-phenoxy]-propionic acid ethyl ester (198 mg, 0.371 mmol), 2-bromopyrimidine (54 mg, 338 mmol), and 5 mL of isopropanol. The flask was purged with N2 three times. After 20 min, palladium acetate (3.0 mg, 0.04 mmol) and triphenylphosphine (3.5 mg, 0.04 mmol) were added. Following addition of a solution of sodium carbonate (43 mg in 1 mL H2O), the mixture was heated to 86° C. for 4 h. The solvent was removed under reduced pressure and the remaining residue taken up in CH2Cl2 (25 mL) and extracted with 0.5 N NaOH (25 mL). The aqueous layer was back extracted with an additional 25 mL CH2Cl2 and the organic layers combined. The organic layer was washed with 1 N NaOH (25 mL) and H2O (25 mL) and then dried and concentrated in vacuo. Flash chromatography provided 45.7 mg (28%) of desired product as a clear oil: 1H NMR (400 MHz, CDCl3) δ8.76 (d, 1 H), 8.45 (d, 2H), 8.06 (d, 2 H), 7.15 (t, 2 H), 6.76 (d, 2 H), 6.71 (d, 2 H), 4.18 (q, 2 H), 4.14 (t, 2 H), 2.93 (t, 2 H), 2.33 (s, 3 H), 1.45 (s, 6 H), 1.21 (t, 3 H); MS (EI) 488.3 (M+H)+.

Workup

  1. customThe flask was purged with N2 three times
  2. customThe solvent was removed under reduced pressure
  3. extractionextracted with 0.5 N NaOH (25 mL)
  4. extractionThe aqueous layer was back extracted with an additional 25 mL CH2Cl2
  5. washThe organic layer was washed with 1 N NaOH (25 mL) and H2O (25 mL)
  6. customdried
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c96c4480b4fb432c876c14d509b821a3
Source dataset
uspto-grants-2003_08
Patent number
US06610696B2

Reaction notes

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