Dichloromethane → (2R)-Methyl 2-((tert-butoxycarbonyl)amino)-3-((tetrahydro-2H-pyran-2-yl)oxy)propanoate

To a 2 L three neck flask fitted with a magnetic stirbar, under argon, was added CH2Cl2 (500 mL), PPTs (pyridinium-p-toluene sulfonate) (2 g, 0.008 mol). After dissolving the PPTs by stirring, N-(tert-butoxycarbonyl)-D-serine methyl ester 1 (97.9 g, 0.446 mol) was added to give a clear yellow solution. DHP (3,4-dihydro-2H-pyran) (105 mL, 1.16 mol) was added in one portion. The clear yellow solution was stirred at room temperature over 60 hr to give a slightly cloudy yellow mixture. The mixture was evaporated to give an off-white solid. Ethyl acetate (650 mL) was added to the residue and stirred for 20 minutes to dissolve. The solution was washed with 1.2M HCl (1×500 mL) to pH 4, sat. NaHCO3 (1×600 mL plus 1λ300 mL) to pH 7, brine (1×500 mL), dried over MgSO4 (20 g), filtered and concentrated under reduced pressure to give 129 g (96%) of product 2 as a waxy white solid. 1H NMR (60 MHz, CDCl3) δ 5.2-5.7 (br m, 1H), 3.4-4.8 (m, 9H), 1.4-1.8 (m, 15H).

1. customto give a clear yellow solution
2. stirringThe clear yellow solution was stirred at room temperature over 60 hr
3. customto give a slightly cloudy yellow mixture
4. customThe mixture was evaporated
5. customto give an off-white solid
6. stirringstirred for 20 minutes
7. dissolutionto dissolve
8. washThe solution was washed with 1.2M HCl (1×500 mL) to pH 4, sat. NaHCO3 (1×600 mL plus 1λ300 mL) to pH 7, brine (1×500 mL)
9. dry with materialdried over MgSO4 (20 g)
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure

ORD record

ord-7c5585eb0a4748d1814f10af34088818

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09340534B2