反応 #48285

反応方程式

(S)—N-((2S,3S)-3,4-bis(tert-butyldimethylsilyloxy)-1-(3-fluorophenyl)butan-2-yl)-2-methylpropane-2-sulfinamide

anisaldehyde

HCl

(BOC)2O

→

desired product

tert-Butyl (2S,3S)-3-(tert-butyldimethylsilyloxy)-1-(3-fluorophenyl)-4-hydroxybutan-2-ylcarbamate

溶媒

EtOH

diethyl ether

反応条件

後処理

1. 1
   workup.STIRRINGto stir for 3 h at 0° C.
2. 2
   その他a white solid formed
3. 3
   その他An LC/Ms was obtained
4. 4
   その他was not removed during the TEA neutralization process
5. 5
   その他Approximately 15 mL of EtOH were removed by rotary evaporator
6. 6
   workup.ADDITIONDCM (10 mL) was added
7. 7
   workup.STIRRINGto stir for 1 h
8. 8
   洗浄The organic layer was washed with ammonium chloride (3×150 mL, sat) and brine
9. 9
   乾燥The organic layer was dried with magnesium sulfate
10. 10
    ろ過filtered
11. 11
    濃縮concentrated
12. 12
    その他to give a colorless crude oil

実験手順

To a 500 mL RBF containing (S)—N-((2S,3S)-3,4-bis(tert-butyldimethylsilyloxy)-1-(3-fluorophenyl)butan-2-yl)-2-methylpropane-2-sulfinamide (2.600 g, 4.9 mmol) was added EtOH (25 ml) and the mixture was allowed to stir at 0° C. for 15 min. At this time, HCl (4N in dioxane) (3.7 ml, 15 mmol) was added via syringe. The reaction was monitored at 1 h by LC/MS 76877-2-1 and tlc (100% EtOAC amino bis TBS; Rf=0.80 UV active stains orange to anisaldehyde amine with primary alcohol deprotected Rf=0.45 to 0.1 streak, UV active and stains white to anisaldehyde). The reaction was allowed to stir for 3 h at 0° C. and then TEA (4.1 ml, 29 mmol) was added fast dropwise and a white solid formed. An LC/Ms was obtained to confirm that the secondary TBS ether was not removed during the TEA neutralization process. Approximately 15 mL of EtOH were removed by rotary evaporator and then DCM (10 mL) was added and the solid went into solution. At this time, (BOC)2O (2.3 ml, 9.8 mmol) was added in one portion and the reaction was allowed to stir for 1 h and then poured into diethyl ether (300 ml). The organic layer was washed with ammonium chloride (3×150 mL, sat) and brine. The organic layer was dried with magnesium sulfate, filtered and concentrated to give a colorless crude oil. The desired product has an Rf=0.40 in 35% EtOAc in hexanes, UV active, stains white to anisaldehyde and purple to moly stain. The crude oil was purified on a 120 g Isco column (10 to 35% EtOAc in hexanes) to give the title compound as a colorless oil.

出典