Hydrochloric Acid → 8-Bromo-1-methyl-1,2,3,4-tetrahydro-1-benzazocin-5-carboxylic acid methylester

HRID 1823253Notes

Reaction equation

HRID 1823253 reaction equation
[CH3:1][O:2][C:3](=[O:19])[CH2:4][CH2:5][CH2:6][CH2:7][N:8]([CH3:18])[C:9]1[CH:14]=[CH:13][C:12]([Br:15])=[CH:11][C:10]=1[CH:16]=O.C[O-].[Na+].Cl>C(=O)(OC)OC.CO>[CH3:1][O:2][C:3]([C:4]1[CH2:5][CH2:6][CH2:7][N:8]([CH3:18])[C:9]2[CH:14]=[CH:13][C:12]([Br:15])=[CH:11][C:10]=2[CH:16]=1)=[O:19]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 10942334Sodium MethoxideHCID 12070457HCID 12070457, compound

Product 1

HCID 865873368-Bromo-1-methyl-1,2,3,4-tetrahydro-1-benzazocin-5-carboxylic acid methylesterYield 31.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 12021Dimethyl CarbonateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 5-(4-bromo-2-formyl-N-methylanilino)pentanoic acid methylester (3.0 g) in dimethyl carbonate (40 ml), a solution of 28% sodium methoxide in methanol (2.3 g) was added at room temperature, and the resulting mixture was stirred at 50° C. for 2 hours. The mixture was allowed to cool to room temperature, and neutralized with 1N hydrochloric acid. After ethyl acetate extraction, the organic layer was washed with saturated salt water, dried over anhydrous sodium sulfate, and concentrated. The concentrate was purified by silica gel column chromatography (h-hexane/ethyl acetate=10/1) and the appropriate eluate was concentrated. The precipitated crystal was washed with IPE and collected by filtration. Drying under reduced pressure (40° C., 1 hour) gave yellow crystal of 8-bromo-1-methyl-1,2,3,4-tetrahydro-1-benzazocin-5-carboxylic acid methylester (0.9 g, yield 31%). mp. 88–89° C. 1H-NMR(CDCl3, δ, 300 MHz): 1.44(2H, m), 2.54(2H, t, J=6.2 Hz), 2.87(3H, s), 3.42(2H, t, J=5.6 Hz), 3.78(3H, s), 6.56(1H, d, J=6.0 Hz), 7.19–7.23(2H, m), 7.68(1H, s). Anal. Calcd for C14 H16 NO2 Br: C,54.21; H,5.20; N,4.52; Br,25.76. Found: C,54.19; H,5.29; N,4.37; Br,25.74. IR(KBr, cm−1): 1689, 1189.

Workup

  1. temperatureto cool to room temperature
  2. extractionAfter ethyl acetate extraction
  3. washthe organic layer was washed with saturated salt water
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customThe concentrate was purified by silica gel column chromatography (h-hexane/ethyl acetate=10/1)
  7. concentrationthe appropriate eluate was concentrated
  8. washThe precipitated crystal was washed with IPE
  9. filtrationcollected by filtration
  10. customDrying under reduced pressure (40° C., 1 hour)

Sources & evidence

ORD record
ord-fc55346518864e9d8f7f1f7fff98344a
Source dataset
uspto-grants-2006_05
Patent number
US07038042B2

Reaction notes

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