Trimethylaluminum → (S)-N-[5-(4-chlorophenoxy)pyrazin-2-yl]-4-hydroxy-4-(3-methoxyphenyl)butanamide

To a stirred solution of 5-(4-chlorophenoxy)pyrazin-2-amine (149 mg, 0.67 mmol) in dry CH2Cl2 (1.5 mL) at room temperature, under argon, is added trimethylaluminum (0.335 mL of a 2.0 N solution in toluene, 0.67 mmol) dropwise. The resulting mixture is stirred for 15 min, then (S)-dihydro-5-(3-methoxyphenyl)furan-2(3H)-one (107 mg, 0.555 mmol) in CH2Cl2 (1.5 mL) is added slowly and stirring is continued at ambient temperature for 3 days. The reaction is quenched carefully with 10% aqueous citric acid (0.5 mL) at 0° C. The mixture is then partitioned between saturated aqueous NaHCO3 (10 mL) and CH2Cl2 (10 mL). The aqueous layer is extracted further with CH2Cl2 (3×10 mL). The combined organic extracts are dried over Na2SO4, filtered, and concentrated in vacuo. The residue is then purified on silica gel (0-75% ethyl acetate in hexane) to give (S)—N-[5-(4-chlorophenoxy)pyrazin-2-yl]-4-hydroxy-4-(3-methoxyphenyl)butanamide (230 mg, 100%) as a white solid.

1. stirringstirring
2. waitis continued at ambient temperature for 3 days
3. customThe reaction is quenched carefully with 10% aqueous citric acid (0.5 mL) at 0° C
4. customThe mixture is then partitioned between saturated aqueous NaHCO3 (10 mL) and CH2Cl2 (10 mL)
5. extractionThe aqueous layer is extracted further with CH2Cl2 (3×10 mL)
6. dry with materialThe combined organic extracts are dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe residue is then purified on silica gel (0-75% ethyl acetate in hexane)

ORD record

ord-fc6dd9d2d74d4158acf3d83199ac9298

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08431607B2