Acetic Acid → methyl 4-[2-(N-benzyloxycarbonyl-N-methylamino)ethylamino]benzoate

HRID 354495Notes

Reaction equation

HRID 354495 reaction equation
[CH2:1]([O:8][C:9]([N:11]([CH2:13][CH:14]=O)[CH3:12])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:16][O:17][C:18](=[O:26])[C:19]1[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=1.CC(O)=O.[BH3-]C#N.[Na+]>C1(C)C=CC=CC=1>[CH2:1]([O:8][C:9]([N:11]([CH2:13][CH2:14][NH:25][C:22]1[CH:21]=[CH:20][C:19]([C:18]([O:17][CH3:16])=[O:26])=[CH:24][CH:23]=1)[CH3:12])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 12082Methyl 4-aminobenzoateHCID 5003444Sodium cyanoborohydrideHCID 12010768Benzyl N-methyl-N-(2-oxoethyl)carbamate

Product 1

HCID 23511696methyl 4-[2-(N-benzyloxycarbonyl-N-methylamino)ethylamino]benzoateYield 334.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A stirred solution of N-benzyloxycarbonyl-N-methylaminoacetaldehyde (1.77 g, 1.1 mmol) in toluene (3 mL) was added methyl-4-aminobenzoate (1.29 g, 8.5 mmol), and the mixture was stirred for 1 hr at room temp. The reaction mixture was evaporated under a reduced pressure and the residue was dissolved into MeCN (15 mL). To the solution was added AcOH (2.44 mL, 43 mmol) and NaBH3CN (2.67 g, 43 mmol), and the resulting mixture was stirred for 15 hr at room temp. The reaction was quenched by the addition of sat. NaHCO3. The mixture was extracted with EtOAc, washed with brine, dried over MgSO4, and evaporated. The residue was chromatographed on silica-gel with n-hexane: EtOAc (7:3, v/v) as eluent to give 1.26 g (43%) methyl 4-[2-(N-benzyloxy carbonyl-N-methylamino)ethylamino]benzoate as a colorless oil. 1H-NMR (CDCl3, 400 MHz) δ2.96 (s, 3H), 3.32 (br m, 2H), 3.50-3.60 (m, 2H), 3.82 (s, 3H), 5.15 (each d, 2H, J=14.6 Hz), 6.35 and 6.58 (m, total 2H), 7.36 (s, 5H), 7.76 and 7.84 (m, total 2H); MS (FAB) m/z 342 (M++1).

Workup

  1. customThe reaction mixture was evaporated under a reduced pressure
  2. dissolutionthe residue was dissolved into MeCN (15 mL)
  3. stirringthe resulting mixture was stirred for 15 hr at room temp
  4. customThe reaction was quenched by the addition of sat. NaHCO3
  5. extractionThe mixture was extracted with EtOAc
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. customevaporated
  9. customThe residue was chromatographed on silica-gel with n-hexane: EtOAc (7:3

Sources & evidence

ORD record
ord-de2aa24645be4fc6b8cef0088cb51523
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

Loading…