p-Toluenesulfonic acid → Methyl N-(tert-butoxycarbonyl)-O-(tetrahydro-2H-pyran-2-yl)-L-serinate

To a stirred solution of methyl N-(tert-butoxycarbonyl)-L-serinate (prepared according to the reported procedure: Bioorg. Med. Chem. 2007, 15, 2860-2867, 10.0 g, 64.27 mmol) in dichloromethane (100 mL), p-toluenesulfonic acid (0.24 g, 1.28 mmol) and 3,4-dihydro-1H-pyran (8.8 mL, 96.67 mmol) were added and the mixture was stirred at the room temperature for 16 hours. The reaction mixture was quenched with saturated sodium bicarbonate solution (50 mL) and extracted with dichloromethane (3×50 mL). The combined organic layers were washed with water (2×50 mL), brine solution (50 mL) and dried over sodium sulfate. Removal of solvent under vacuum and also high vacuum to remove excess 3,4-dihydro-1H-pyran. The residue was dissolved in ethyl acetate (10 mL) and pet. ether (100 mL) was added over it was stirred for 10 minutes. The solid obtained was filtered and washed with pet. ether (50 mL). Yield: 12.0 g (78%). 1H NMR (400 MHz, DMSO-d6) δ: 1.33-1.34 (m, 1H), 1.39 (s, 9H), 1.41-1.68 (m, 6H), 3.41-3.45 (m, 1H), 3.55-3.59 (m, 1H), 3.61 (s, 3H), 3.81-3.84 (m, 1H), 4.23-4.28 (m, 1H), 4.58 (br s, 1H), 7.15 (d, 1H).

1. customThe reaction mixture was quenched with saturated sodium bicarbonate solution (50 mL)
2. extractionextracted with dichloromethane (3×50 mL)
3. washThe combined organic layers were washed with water (2×50 mL), brine solution (50 mL)
4. dry with materialdried over sodium sulfate
5. customRemoval of solvent under vacuum and also high vacuum
6. customto remove excess 3,4-dihydro-1H-pyran
7. dissolutionThe residue was dissolved in ethyl acetate (10 mL)
8. additionpet. ether (100 mL) was added over it
9. stirringwas stirred for 10 minutes
10. customThe solid obtained
11. filtrationwas filtered
12. washwashed with pet. ether (50 mL)

ORD record

ord-ba1ec8c51d6e463db52ebc7997969c84

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08889671B2