Methanol → Hexanamide, N,N-diethyl-

To a solution of R-29 (3.5 mmol, 1.00 g) dissolved in 10:1 (V:V) Et2O:MeOH (40 mL) is added TMS diazomethane (0.5M in THF, 13 mmol, 6.4 mL). The mixture is stirred at ambient temperature for 4 h. The reaction is concentrated in vacuo and the residue is dissolved in 4 N HCl in dioxane (5 mL) and stirred at ambient temperature for 4 h then concentrated in vacuo to give R-30. To a solution of R-30 (4.0 mmol, 0.78 g) and dibromothiazole (2.7 mmol, 0.65 g) in DMF (10 mL) is added triethylamine (10 mmol, 1.5 mL). The solution is heated at 80° C. for 16 h. The reaction is concentrated in vacuo and the residue is purified by flash chromatography to give R-31 (0.66 g, 60%). A solution of R-31 (2.4 mmol, 0.76 g), 4-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (2.9 mmol, 0.67 g) in THF (20 mL) and 2 M aqueous Na2CO3 (9 mmol, 4.5 mL) is sparged with argon. Tetrakistriphenylphosphinepalladium(0) (0.24 mmol, 0.28 g) is added and the mixture is heated at 80° C. for 16 h. The mixture is cooled then diluted with DCM and passed through a hydrophobic frit. The organics are concentrated in vacuo and the residue is purified by flash chromatography to give the title intermediate (0.68 g, 82%).

1. concentrationThe reaction is concentrated in vacuo
2. dissolutionthe residue is dissolved in 4 N HCl in dioxane (5 mL)
3. stirringstirred at ambient temperature for 4 h
4. concentrationthen concentrated in vacuo
5. customto give R-30
6. temperatureThe solution is heated at 80° C. for 16 h
7. concentrationThe reaction is concentrated in vacuo
8. customthe residue is purified by flash chromatography

ORD record

ord-961296a2b0974e15b11533ddfb1fc01b

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08815857B2