1,2-Dichloroethane → n-Methoxy-n-methyl(4-{[(phenylmethoxy)carbonylamino]-methyl}phenyl)carboxamide

HRID 532098

Reaction equation

HRID 532098 reaction equation
[C:1]1([CH2:7][O:8][C:9]([NH:11][CH2:12][C:13]2[CH:21]=[CH:20][C:16]([C:17]([OH:19])=O)=[CH:15][CH:14]=2)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1C=C[C:25]2[N:30]([OH:31])N=NC=2C=1.[CH3:32]CN(C(C)C)C(C)C.C(Cl)CCl.Cl.COCN>CN(C=O)C>[CH3:32][O:31][N:30]([CH3:25])[C:17]([C:16]1[CH:15]=[CH:14][C:13]([CH2:12][NH:11][C:9]([O:8][CH2:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[O:10])=[CH:21][CH:20]=1)=[O:19]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 14799974-((((Benzyloxy)carbonyl)amino)methyl)benzoic acidHCID 21959107Methoxymethanamine hydrochloride

Product 1

HCID 57903228n-Methoxy-n-methyl(4-{[(phenylmethoxy)carbonylamino]-methyl}phenyl)carboxamideYield 85.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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.

Workup

  1. customthen partitioned between EtOAc and 0.1 M citric acid (100 mL each) with transfer to a separatory funnel
  2. customThe layers separated
  3. washthe aqueous layer washed with EtOAc (2×50 mL)
  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. dry with materialthen dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by chromatography on silica (40×250 mm)
  9. washa gradient elution from 1:1→3:7 pentane/EtOAc (Rf=0.3 in 1:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-a31a09e9479b4da194aa38d2178b33e9
Source dataset
uspto-grants-2014_10
Patent number
US08852553B2

Linked notes

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