Dimethyl Sulfoxide → tert-Butyl (5-formylpyridin-2-yl)carbamate

To a solution of methyl-6-(tert-butoxycarbonylamino)-nicotinate (2.20 g, 8.72 mmol) in anhydrous THF (50 mL), cooled to -30° C. was added DIBAL-H (1.0M in hexane, 34. 8 mL, 34.8 mmol) dropwise. After 1 h, 40 mL of a saturated solution of Rochelle salts was added and stirred vigorously for 10 h. The volatiles were removed in vacuo and the aqueous layer was extracted with methylene chloride (3×50 mL). The organic layer was washed with water (1×50 mL) and brine (1×50 mL), dried over MgSO4, filtered, and concentrated in vacuo. The residue was used directly in the next step. To a solution of oxalyl chloride (4.12 g, 32.46 mmol) in methylene chloride (30 mL), cooled to -78° C., was added DMSO (2.54 g, 32.46 mmol) dissolved in methylene chloride (9 mL) dropwise. After 20 minutes, the crude alcohol (1.82 g, 8.11 mmol) dissolved in 35 mL of methylene chloride was added followed by triethylamine (4.92 g, 48.66 mmoL). The ice bath was removed and the reaction stirred for 1 hr at rt, then water (30 mL) was added. The layers were separated and the aqueous layer was extracted with methylene chloride (2×50 mL). The organic layer was washed with water (1×50 mL) and brine (1×50 mL), dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (30×150 mm column of SiO2, EtOAc/methylene chloride 1:11) to give the title compound as a colorless solid:

1. customThe volatiles were removed in vacuo
2. extractionthe aqueous layer was extracted with methylene chloride (3×50 mL)
3. washThe organic layer was washed with water (1×50 mL) and brine (1×50 mL)
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. waitAfter 20 minutes
8. additionwas added
9. customThe ice bath was removed
10. stirringthe reaction stirred for 1 hr at rt
11. additionwater (30 mL) was added
12. customThe layers were separated
13. extractionthe aqueous layer was extracted with methylene chloride (2×50 mL)
14. washThe organic layer was washed with water (1×50 mL) and brine (1×50 mL)
15. dry with materialdried over MgSO4
16. filtrationfiltered
17. concentrationconcentrated in vacuo
18. customThe residue was purified by flash column chromatography (30×150 mm column of SiO2, EtOAc/methylene chloride 1:11)

ORD record

ord-fe1daf39ae4d4b35afe7ff5913ebb1eb

Source dataset

uspto-grants-1999_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05866573