Reaction #168755

Reaction equation

hexane EtOH

mesyl chloride

(S)-2-(5-bromo-2-fluoro-phenyl)-propane-1,2-diol

HCl

→

(S)-2-(5-Bromo-2-fluoro-phenyl)-2-methyl-oxirane

Solvents

hexane EtOAc

CH2Cl2

Conditions

Workup

1. 1
   Otherat 0-5° C
2. 2
   Extractionextracted with CH2Cl2
3. 3
   WashCombined extracts were washed with 1N HCl, H2O and saturated NaHCO3 solution
4. 4
   Dryingdried over MgSO4
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated
7. 7
   workup.DISSOLUTIONThe crude mesylate was dissolved in TBME (500 ml)
8. 8
   workup.STIRRING200 ml 2N aqueous NaOH and after stirring for 2 h at 25° C. the mixture
9. 9
   Extractionwas extracted with TBME
10. 10
    WashCombined extracts were washed with NaH2PO4 solution and brine
11. 11
    Dryingdried over MgSO4
12. 12
    Filtrationfiltered
13. 13
    Concentrationconcentrated
14. 14
    Otherto provide the (S)-enantiomer as a colorless oil
15. 15
    OtherHPLC RtH5=1.186 min

Procedure

To a solution of (S)-2-(5-bromo-2-fluoro-phenyl)-propane-1,2-diol (37.35 g, 150 mmol) in CH2Cl2 (400 ml) was added under argon NEt3 (41.8 ml, 300 mmol) and dropwise mesyl chloride (12.8 ml, 165 mmol) at 0-5° C. After stirring for 0.5 h at 0-5° C. the reaction mixture was added to cold 1N HCl and extracted with CH2Cl2. Combined extracts were washed with 1N HCl, H2O and saturated NaHCO3 solution, dried over MgSO4, filtered and concentrated. The crude mesylate was dissolved in TBME (500 ml) and 200 ml 2N aqueous NaOH and after stirring for 2 h at 25° C. the mixture was extracted with TBME. Combined extracts were washed with NaH2PO4 solution and brine, dried over MgSO4, filtered and concentrated to provide the (S)-enantiomer as a colorless oil: 78% ee (Chiralpak AS-H 1218, hexane-EtOH 97:3, 0.4 mL/min); TLC (hexane-EtOAc 3:1): Rf=0.69; HPLC RtH5=1.186 min; 1H NMR (360 MHz, CDCl3): δ 7:46 (dd, 1H), 7.30 (m, 1H), 6.83 (dd, 1H), 2.88 (d, 1H), 2.72 (d, 1H), 1.59 (s, 3H).

Source