反应详情

Under a nitrogen atmosphere, suspend (2S)-2-(4-fluorophenyl)morpholine hydrochloride (29.5 g, 128.8 mmol) in DCM (17 L) at 22° C. and add triethylamine (35.89 mL, 257.5 mmol). Add N-[(1R)-1-(4-formylphenyl)ethyl]methanesulfonamide (29.26 g, 128.8 mmol) and stir the resulting solution for 30 min. Add acetic acid (8.85 mL, 154.5 mmol), then sodium triacetoxyborohydride (86.17 g, 386.3 mmol) portion-wise in 3 batches. Stir for 3 h; monitor the reaction via LCMS until completion. Quench the reaction via the slow addition of a saturated aqueous solution of sodium bicarbonate (259.31 mL) to give a solution with a pH of 8. Separate the layers, and extract the aqueous layer with 200 mL DCM. Combine the organic layers, wash with saturated sodium bicarbonate, water, brine, and then dry over MgSO4. Filter; collect the filtrate; and concentrate to give a residue. Purify the residue via silica gel flash column chromatography, using a gradient of 100% DCM to DCM:MeOH (95:5). Combine the product fractions, and concentrate to provide the title product as a yellow thick oil (41 g, 81.13%). MS (m/z): 393 (M+1)

1. customat 22° C.
2. customthe reaction via LCMS until completion
3. customQuench
4. customthe reaction
5. customto give a solution with a pH of 8
6. customSeparate the layers
7. extractionextract the aqueous layer with 200 mL DCM
8. washwash with saturated sodium bicarbonate, water, brine
9. dry with materialdry over MgSO4
10. filtrationFilter
11. customcollect the filtrate
12. concentrationand concentrate
13. customto give a residue
14. customPurify the residue via silica gel flash column chromatography
15. concentrationCombine the product fractions, and concentrate