反应详情

Dissolve oxalyl chloride (18.4 mL, 211 mmol) in CH2Cl2 (1000 mL), cool below −70° C., and add DMSO (18.0 mL, 253 mmol) via syringe pump over 30 min. Stir for 45 min, and then add portionwise a suspension of trans-(4-hydroxy-cyclohexyl)-carbamic acid benzyl ester (35.00 g, 140 mmol) in CH2Cl2 (1000 mL), while maintaining the temperature below −70° C. Add the suspension by removing a stopper from the reaction flask and quickly pouring in as much of the suspension as possible while keeping the temperature below −70° C., resulting in a slightly turbid solution upon complete addition. Stir the reaction for 90 min, then add triethylamine (97.8 mL, 702 mmol) slowly via syringe. Stir for another hour, and allow the reaction to slowly warm to room temperature overnight. Wash sequentially with water (1500 mL), brine (2×1500 mL), and saturated aqueous NaHCO3 (2×1500 mL). Separate the organic portion and dry (MgSO4), filter, and concentrate under reduced pressure. Triturate the crude residue twice with 4:1 Hexane/EtOAc (500 mL, then 250 mL). (Alternatively, triturate with 15% EtOAc/Hexane. Then only one trituration is required.) Filter and collect the solids and dry at 35° C. in a vacuum oven to obtain 26.44 g of the product. Combine the filtrates of the triturations and concentrate under reduced pressure, followed by trituration of the residue in 9:1 hexane/EtOAc (100 mL) to afford a second crop of 5.70 g, for a combined yield of 32.14 g (93%). ESI MS: m/z 248 [C14H17NO3+H]+; 1H NMR (300 MHz, CDCl3): δ 1.63-1.78 (m, 2H), 2.22-2.27 (m, 2H), 2.32-2.49 (m, 4H), 3.95-4.04 (m, 1H), 4.75 (br s, 1H), 5.11 (s, 2H), 7.29-7.42 (m, 5H)

1. temperaturecool below −70° C.
2. additionadd portionwise
3. temperaturewhile maintaining the temperature below −70° C
4. additionAdd the suspension
5. customby removing a stopper from the reaction flask
6. additionquickly pouring in as much of the suspension as possible
7. customthe temperature below −70° C.
8. customresulting in a slightly turbid solution upon complete addition
9. stirringStir
10. customthe reaction for 90 min
11. stirringStir for another hour
12. customthe reaction
13. washWash sequentially with water (1500 mL), brine (2×1500 mL), and saturated aqueous NaHCO3 (2×1500 mL)
14. customSeparate the organic portion
15. dry with materialdry (MgSO4)
16. filtrationfilter
17. concentrationconcentrate under reduced pressure
18. customTriturate the crude residue twice with 4:1 Hexane/EtOAc (500 mL
19. custom(Alternatively, triturate with 15% EtOAc/Hexane
20. filtration) Filter
21. customcollect the solids
22. customdry at 35° C. in a vacuum oven