Methanol → t-Butyl 2-(2-bromo-4-((methylamino)methyl)phenoxy)acetate

t-Butyl 2-(2-bromo-4-formylphenoxy)acetate (1) (10.11 g, 32.1 mmol, 1 eq) was dissolved in a 2 M solution of methylamine in methanol (30 mL, 60 mmol, 1.9 eq) and stirred at room temperature for 4 h. The solvent and excess methylamine were removed in vacuo and the resultant imine was dissolved in anhydrous methanol (200 mL). Sodium Borohydride (2.4 g) was added slowly under argon and the mixture was stirred for 2 h. Saturated NaHCO3 (100 mL) was added and allowed to stir for 15 minutes at which point the methanol was removed in vacuo. The resultant aqueous mixture was extracted with DCM (2×50 mL) and the combined organic layers were washed with brine (100 mL), dried (Na2SO4) and concentrated in vacuo to yield 6.2 g (58%) of t-butyl 2-(2-bromo-4-((methylamino)methyl)phenoxy)acetate (2). 1HNMR (CDCl3, 300 MHz): δ 7.50 (d, 1H), 7.15 (m, 1H), 6.72 (d, 1H), 4.55 (s, 2H), 3.65 (s, 2H), 2.41 (s, 3H), 1.45 (s, 9H).

1. customThe solvent and excess methylamine were removed in vacuo
2. dissolutionthe resultant imine was dissolved in anhydrous methanol (200 mL)
3. additionSodium Borohydride (2.4 g) was added slowly under argon
4. stirringthe mixture was stirred for 2 h
5. additionSaturated NaHCO3 (100 mL) was added
6. stirringto stir for 15 minutes at which point the methanol
7. customwas removed in vacuo
8. extractionThe resultant aqueous mixture was extracted with DCM (2×50 mL)
9. washthe combined organic layers were washed with brine (100 mL)
10. dry with materialdried (Na2SO4)
11. concentrationconcentrated in vacuo

ORD record

ord-1b789ae38b234d58aeed766f05f81588

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08822467B2