Potassium Phosphate, Tribasic → 4-(6-Dimethylcarbamoyl-pyridin-3-yloxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid methyl ester

HRID 1643608Notes

Reaction equation

HRID 1643608 reaction equation
[CH3:1][N:2]([CH3:12])[C:3]([C:5]1[CH:10]=[CH:9][C:8](Br)=[CH:7][N:6]=1)=[O:4].[CH3:13][O:14][C:15]([C:17]1[CH:27]=[C:26]([OH:28])[C:20]2[CH2:21][C:22]([CH3:25])([CH3:24])[O:23][C:19]=2[CH:18]=1)=[O:16].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:13][O:14][C:15]([C:17]1[CH:27]=[C:26]([O:28][C:8]2[CH:7]=[N:6][C:5]([C:3](=[O:4])[N:2]([CH3:12])[CH3:1])=[CH:10][CH:9]=2)[C:20]2[CH2:21][C:22]([CH3:25])([CH3:24])[O:23][C:19]=2[CH:18]=1)=[O:16]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 228316185-bromo-N,N-dimethylpicolinamideHCID 25067323Methyl 4-hydroxy-2,2-dimethyl-2,3-dihydro-1-benzofuran-6-carboxylate

Product 1

HCID 595602244-(6-Dimethylcarbamoyl-pyridin-3-yloxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid methyl esterYield 13%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5-bromo-pyridine-2-carboxylic acid dimethylamide (161a) (1.14 g, 4.95 mmol), 4-hydroxy-2,2-dimethyl-2,3-dihydrobenzofuran-6-carboxylic acid methyl ester (3e) (1.10 g, 4.95 mmol), and K3PO4 (2.10 g, 9.91 mmol), 2-di-t-butylphosphino-2′,4′,6′-tri-i-propyl-1,1′-biphyl (210 mg, 0.495 mmol), and Pd(OAc)2 (111 mg, 0.495 mmol) in toluene (10 mL) was heated to 100° C. in a microwave for 6 hr, cooled to room temperature, filtered through celite, washed with EtOAc, concentrated, and purified by Biotage column chromatography with 35-70% EtOAc in hexanes to give a white foam (238 mg, 13% yield). 1H NMR (400 MHz, CDCl3) δ 8.32 (d, J=2.78 Hz, 1 H) 7.70 (d, J=8.59 Hz, 1 H) 7.31 (dd, J=8.72, 2.91 Hz, 1 H) 7.25 (d, J=1.26 Hz, 1 H) 7.19 (d, J=1.26 Hz, 1 H) 3.87 (s, 3 H) 3.15 (d, J=4.29 Hz, 6 H) 2.92 (s, 2 H) 1.49 (s, 6 H); LCMS for C20H22N2O5 m/z 371.20 (M+H+).

Workup

  1. temperaturecooled to room temperature
  2. filtrationfiltered through celite
  3. washwashed with EtOAc
  4. concentrationconcentrated
  5. custompurified by Biotage column chromatography with 35-70% EtOAc in hexanes

Sources & evidence

ORD record
ord-904043f9053649ae8b4df03980ac1ed5
Source dataset
uspto-grants-2012_02
Patent number
US08119624B2

Reaction notes

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