Reaction #511553

Reaction equation

(i-PrO)3B

HCl

5b

2-Bromo-5-fluoro-[1-(methoxymethoxy)methyl]benzene

n-butyllithium

→

19b

Yield 60.4%

1,3-Dihydro-5-fluoro-1-hydroxy-2,1-benzoxaborole

Yield 60.4%

Solvents

Water

THF

Conditions

Workup

1. 1
   OtherAnion precipitated
2. 2
   Otherthe solvent was removed under reduced pressure to about a half volume
3. 3
   workup.ADDITIONThe mixture was poured into ethyl acetate and water
4. 4
   WashThe organic layer was washed with brine
5. 5
   Dryingdried over anhydrous Na2SO4
6. 6
   OtherThe solvent was removed under reduced pressure
7. 7
   workup.ADDITIONTo a solution of the residue in tetrahydrofuran (360 mL) was added 6 N HCl (90 mL)
8. 8
   OtherThe solvent was removed under reduced pressure to about a half volume
9. 9
   workup.ADDITIONThe mixture was poured into ethyl acetate and water
10. 10
    WashThe organic layer was washed with brine
11. 11
    Dryingdried over anhydrous Na2SO4
12. 12
    OtherThe solvent was removed under reduced pressure
13. 13
    workup.ADDITIONthe residue was treated with i-Pr2O/hexane

Procedure

To a solution of 5b (73.2 g, 293 mmol) in dry THF (400 mL) was added n-butyllithium (1.6 M in hexanes; 200 mL) over 45 min at −78° C. under nitrogen atmosphere. Anion precipitated. After 5 min, (i-PrO)3B (76.0 mL, 330 mmol) was added over 10 min, and the mixture was allowed to warm to room temperature over 1.5 h. Water and 6 N HCl (55 mL) were added, and the solvent was removed under reduced pressure to about a half volume. The mixture was poured into ethyl acetate and water. The organic layer was washed with brine and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure. To a solution of the residue in tetrahydrofuran (360 mL) was added 6 N HCl (90 mL), and the mixture was stirred at 30° C. overnight. The solvent was removed under reduced pressure to about a half volume. The mixture was poured into ethyl acetate and water. The organic layer was washed with brine and dried over anhydrous Na2SO4. The solvent was removed under reduced pressure, and the residue was treated with i-Pr2O/hexane to give 19b (26.9 g, 60%) as a white powder: mp 118-120° C.; 1H NMR (300 MHz, DMSO-d6) δ (ppm) 4.95 (s, 2H), 7.15 (m, 1H), 7.24 (dd, J=9.7, 1.8 Hz, 1H), 7.74 (dd, J=8.2, 6.2 Hz, 1H), 9.22 (s, 1H); ESI-MS m/z 151 (M−H)−; HPLC purity 97.8%; Anal (C7H6BFO2) C, H.

Source