Reaktion #51491

Reaktionsgleichung

tert-butyl (1S)-3-chloro-1-(3,5-difluorobenzyl)-2-oxopropylcarbamate

THF

sodium borohydride

→

title compound

tert-butyl (1S,2S)-3-chloro-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate

Lösungsmittel

ethanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeTo a 250 mL 3-neck round bottom flask equipped with magnetic stir bar, nitrogen inlet
2. 2
   Temperaturthen cooled to −78°
3. 3
   TemperaturOnce the mixture is cooled
4. 4
   Sonstigethe internal temperature below −70°
5. 5
   workup.ADDITIONOnce this addition
6. 6
   Temperaturthen warmed to 0°
7. 7
   workup.STIRRINGstirred an additional 1 hr
8. 8
   SonstigeThe mixture is quenched by the addition of saturated potassium bisulfate (15 mL) and water (15 mL)
9. 9
   workup.STIRRINGThis slurry is stirred for 30 min at 20-250
10. 10
    Einengenthen concentrated under reduced pressure to half its volume
11. 11
    TemperaturThe mixture is then cooled to 0°
12. 12
    workup.STIRRINGstirred for 30 min
13. 13
    FiltrationAfter this time, the resultant solids are collected by filtration
14. 14
    Waschenwashed with water (2×50 mL)
15. 15
    Sonstigethen dried under reduced pressure at 500
16. 16
    Sonstigeto give crude product
17. 17
    SonstigeThe desired product is recrystallized from hexanes/ethanol (25/1)

Vorschrift

To a 250 mL 3-neck round bottom flask equipped with magnetic stir bar, nitrogen inlet and thermocouple, is added tert-butyl (1S)-3-chloro-1-(3,5-difluorobenzyl)-2-oxopropylcarbamate (III, EXAMPLE 2, 4.4 g, 0.0132 moles, 1 equivalent) followed by THF (20 mL) and ethanol (30 mL) then cooled to −78°. Once the mixture is cooled, sodium borohydride (2.0 g, 0.0527 moles, 4 equivalents) is added as a solid portion wise over 30 min keeping the internal temperature below −70°. Once this addition is complete, the contents are stirred for 2 hr at −78° then warmed to 0° and stirred an additional 1 hr. The mixture is quenched by the addition of saturated potassium bisulfate (15 mL) and water (15 mL). This slurry is stirred for 30 min at 20-250 then concentrated under reduced pressure to half its volume. The mixture is then cooled to 0° and stirred for 30 min. After this time, the resultant solids are collected by filtration and washed with water (2×50 mL) then dried under reduced pressure at 500 to give crude product. A syn/anti ratio of 4-9:1 has been observed. The desired product is recrystallized from hexanes/ethanol (25/1) to give the title compound, mp=149°; NMR (DMSO-d6) δ 6.89-7.16, 5.61, 3.64-3.83, 3.19, 2.69 and 1.41; CMR (DMSO-d6) δ 163.67, 161.24, 155.44, 112.70, 101.55, 78.04, 72.99, 54.29, 48.24, 35.97 and 28.37.

Quelle