Acetic Acid → N-(4-bromobenzyl)-2-methoxyethanamine

HRID 2101210Notes

Reaction equation

HRID 2101210 reaction equation
COCCN.[Br:6][C:7]1[CH:18]=[CH:17][C:10]([CH2:11][NH:12][CH2:13][CH2:14][O:15][CH3:16])=[CH:9][CH:8]=1.BrC1C=CC(C=O)=CC=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.[O-]S([O-])(=O)=O.[Mg+2]>[Br:6][C:7]1[CH:8]=[CH:9][C:10]([CH2:11][NH:12][CH2:13][CH2:14][O:15][CH3:16])=[CH:17][CH:18]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 707414-BromobenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 86760933HCID 86760933, compound

Product 1

HCID 4402900N-(4-bromobenzyl)-2-methoxyethanamine

Reagents, catalysts & solvents 2

HCID 24083Sulfuric acid magnesium salt (1:1)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-bromo-1,1,1-trifluoroethane (0.74 ml) and triethylamine (1.13 ml) in DMF (30 ml) was added (4-bromobenzyl)-(2-methoxyethyl)amine (2.05 g). The resulting mixture was stirred for 18 h. The mixture was partitioned between ethyl acetate and water, the organic layer was dried and evaporated to an oil, which was purified by column chromatography eluting with a gradient of ethyl acetate (60 to 100%) in isohexane to give (4-bromobenzyl)-(2-methoxyethyl)-(2,2,2-trifluoroethyl) amine (1.84 g). 1H NMR (DMSO-D6) δ 2.1 (bs, 2H), 2.6 (t, 2H), 3.2 (s, 3H), 3.4 (t, 2H), 3.65 (d, 2H), 7.25 (d, 2H), 7.45 (d, 2H). c) (4-Bromobenzyl)-(2-methoxyethyl)amine 2-Methoxyethylamine (16 ml) was added to a solution of 4-bromobenzaldehyde (17.2 g) in THF (150 ml). Glacial acetic acid (5.32 ml) and MgSO4 (0.5 g) were added and the mixture was stirred for 45 min. Sodium triacetoxyborohydride (29.7 g) was added and the resulting mixture was stirred for 4 h. The mixture was partitioned between ethyl acetate and saturated sodium bicarbonate. The organic layer was dried and concentrated to an oil, which was purified by column chromatography, eluting with a gradient of ethyl acetate (10 to 100%) in isohexane, then eluting with methanol/DCM (10:90) to give (4-bromobenzyl)-(2-methoxyethyl)amine (13.0 g) as a yellow oil. MS (ES) 244 (M+H)+. 1H NMR (DMSO-D6) δ 2.05 (bs, 1H), 2.6 (t, 2H), 3.38 (t, 2H), 3.2 (s, 3H), 3.62 (s, 2H), 7.25 (d, 2H), 7.45 (d, 2H).

Workup

  1. stirringthe resulting mixture was stirred for 4 h
  2. customThe mixture was partitioned between ethyl acetate and saturated sodium bicarbonate
  3. customThe organic layer was dried
  4. concentrationconcentrated to an oil, which
  5. customwas purified by column chromatography
  6. washeluting with a gradient of ethyl acetate (10 to 100%) in isohexane
  7. washeluting with methanol/DCM (10:90)

Sources & evidence

ORD record
ord-6ca0bd9ebdfc45089d8c7c70c8277377
Source dataset
uspto-grants-2009_08
Patent number
US07572826B2

Reaction notes

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