Dimethyl Sulfoxide → [(Z)-4-((R)-2-formyl-6-oxo-piperidin-1-yl)-but-2-enyloxy]-acetic acid methyl ester

Trifluoroacetic anhydride (0.24 mL, 1.70 mmol) was added to a solution of DMSO (0.14 mL, 1.97 mmol) in CH2Cl2 (2 mL) at −78° C. After 15 min at −78° C., a solution of [(Z)-4-((R)-2-hydroxymethyl-6-oxo-piperidin-1-yl)-but-2-enyloxy]acetic acid methyl ester (from example 1, step 3, 220 mg, 0.81 mmol) in CH2Cl2 (1.5 mL) was added via cannula. After 20 min at −78° C., triethylamine (0.33 mL, 2.37 mmol) was added and the reaction mixture was allowed to warm to rt. After 1 h at rt, the reaction was quenched with saturated aqueous NH4Cl (15 mL) and the mixture was extracted with CH2Cl2 (3×15 mL). The combined organic phase was dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (10% →50% EtOAc/CH2Cl2, gradient) afforded 150 mg (69%) of [(Z)-4-((R)-2-formyl-6-oxo-piperidin-1-yl)-but-2-enyloxy]-acetic acid methyl ester.

1. waitAfter 20 min at −78° C.
2. waitAfter 1 h at rt
3. customthe reaction was quenched with saturated aqueous NH4Cl (15 mL)
4. extractionthe mixture was extracted with CH2Cl2 (3×15 mL)
5. dry with materialThe combined organic phase was dried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customPurification of the residue by flash column chromatography on silica gel (10% →50% EtOAc/CH2Cl2, gradient)

ORD record

ord-e0e63d53e5b947398c6677744fe8644c

Source dataset

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07179820B2