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

Temperature

0 °C

A solution of oxalyl chloride (0.15 mL, 1.76 mmol) in CH2Cl2 (1.0 mL) was added to a solution of DMSO (0.16 mL, 2.25 mmol) in CH2Cl2 (1.0 mL) at −78° C. After 15 min at −78° C., a solution of [4-((R)-2-hydroxymethyl-6-oxo-piperidin-1-yl)-butoxy]-acetic acid methyl ester (240 mg, 0.88 mmol) in CH2Cl2 (1.5 mL) was added via cannula. After 20 min at −78° C., triethylamine (0.37 mL, 2.65 mmol) was added. After 20 min at −78° C., the mixture was allowed to warm to 0° C. After 30 min at 0° C., the reaction was allowed to warm to rt. After 45 min at rt, saturated aqueous NaHCO3 (15 mL) was added 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 (40% →70% EtOAc/CH2Cl2, gradient) afforded 96 mg (40%) of [4-((R)-2-formyl-6-oxo-piperidin-1-yl)-butoxy]-acetic acid methyl ester.

1. waitAfter 20 min at −78° C.
2. waitAfter 20 min at −78° C.
3. waitAfter 30 min at 0° C.
4. temperatureto warm to rt
5. waitAfter 45 min at rt
6. extractionthe mixture was extracted with CH2Cl2 (3×15 mL)
7. dry with materialThe combined organic phase was dried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customPurification of the residue by flash column chromatography on silica gel (40% →70% EtOAc/CH2Cl2, gradient)

ORD record

ord-19e4e3a287134ee2aef29e08b88fa0b9

Source dataset

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07179820B2