Reaction #1904059

Reaction equation

hydrochloride

2-amino-5-bromobenzoic acid

methylmagnesium bromide

ether

sodium hydroxide

→

2-(2-amino-5-bromophenyl)propan-2-ol

Yield 57.0%

Solvents

ethyl acetate

THF

Conditions

Workup

1. 1
   workup.ADDITIONwas added
2. 2
   OtherThe organic layer was separated
3. 3
   Extractionaqueous layer was extracted with ethyl acetate (3×100 mL)
4. 4
   WashThe combined organic layers were washed with brine
5. 5
   Dryingdried (MgSO4)
6. 6
   OtherAfter removal of solvent in vacuo
7. 7
   Otherthe residue was purified by a silica gel flash chromatography (hexane:ethyl acetate/3:2)

Procedure

A solution of 2-amino-5-bromobenzoic acid (10 g, 46 mmol) in dry THF (200 mL) was treated at −78° C. under nitrogen with a solution of methylmagnesium bromide in ether (3.0 M, 90 mL, 270 mmol). The reaction mixture was slowly warmed to ambient temperature, kept stirring for 48 hours under nitrogen and then poured into a cold 0.5 N aqueous hydrochloride solution (300 mL). The mixture was neutralized with aqueous 1 N sodium hydroxide solution and ethyl acetate (300 mL) was added. The organic layer was separated and aqueous layer was extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with brine and dried (MgSO4). After removal of solvent in vacuo, the residue was purified by a silica gel flash chromatography (hexane:ethyl acetate/3:2) to give 2-(2-amino-5-bromophenyl)propan-2-ol as off-white solid (6 g, 57%): mp 62-63° C.; 1H-NMR (CDCl3) δ 7.19 (d, 1H, J=2.3 Hz), 7.12 (dd, 1H, J=8.4, 2.3 Hz), 6.51 (d, 1H, J=8.4 Hz), 4.70 (s, 2H), 1.82 (s, 1H), 1.65 (s, 6H).

Source