Reaction #417909

Reaction equation

4-{[(phenylmethoxy)carbonylamino]methyl}benzoic acid

HOBt

i-Pr2NEt

EDC

methoxymethylamine hydrochloride

→

material

Yield 85.9%

N-methoxy-N-methyl(4-{[(phenylmethoxy)carbonylamino]-methyl}phenyl)carboxamide

Yield 85.9%

Solvents

DMF

Conditions

Workup

1. 1
   Otherthen partitioned between EtOAc and 0.1 M citric acid (100 mL each) with transfer to a separatory funnel
2. 2
   OtherThe layers separated
3. 3
   Washthe aqueous layer washed with EtOAc (2×50 mL)
4. 4
   WashThe combined EtOAc layers were successively washed with 0.1 M citric acid, 0.1 M NaOH and saturated aqueous NaCl (3×50 mL each)
5. 5
   Dryingthen dried over MgSO4
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated in vacuo
8. 8
   OtherPurification by chromatography on silica (40×250 mm)
9. 9
   Washa gradient elution from 1:1→3:7 pentane/EtOAc (Rf=0.3 in 1:1 hexanes/EtOAc)

Procedure

A solution of 4-{[(phenylmethoxy)carbonylamino]methyl}benzoic acid (3.99 g, 14.0 mmol; Groves, K.; Wilson, A. J.; Hamilton, A. D. J. Am. Chem. Soc. 2004, 126(40), 12833-12842.) and HOBt (2.57 g, 16.8 mmol) in dry DMF (70.0 mL) was successively treated with i-Pr2NEt (4.87 mL, 28.0 mmol) and EDC (3.22 g, 16.8 mmol) at 22° C. After 0.25 h, the solution was treated with methoxymethylamine hydrochloride (1.64 g, 16.8 mmol) in one portion. The resulting mixture was stirred 1 h then partitioned between EtOAc and 0.1 M citric acid (100 mL each) with transfer to a separatory funnel. The layers separated and the aqueous layer washed with EtOAc (2×50 mL). The combined EtOAc layers were successively washed with 0.1 M citric acid, 0.1 M NaOH and saturated aqueous NaCl (3×50 mL each) then dried over MgSO4, filtered and concentrated in vacuo. Purification by chromatography on silica (40×250 mm) using a gradient elution from 1:1→3:7 pentane/EtOAc (Rf=0.3 in 1:1 hexanes/EtOAc) afforded pure material as a colorless oil (3.94 g, 12.0 mmol; 85.9%). 1H NMR (CDCl3, 300 MHz): δ 7.63 (2H, AA′BB′, JAB=8.3 Hz, JAA′=1.9 Hz), 7.36-7.27 (7H, m), 5.20 (1H, brs), 5.13 (2H, s), 4.40 (2H, brd, J=6.0 Hz), 3.52 (3H, s), 3.33 (3H, s). 13C NMR (CDCl3, 75 MHz): δ 169.5, 156.4, 141.1, 136.4, 133.2, 128.6, 128.5, 128.1, 128.1, 126.9, 66.9, 61.0, 44.8, 33.7. HRMS calcd for C18H20N2O4: 329.1496. Found: 329.1497.

Source