1,2-Dichloroethane → Racemic benzyl 1-(3-bromo-2-methylphenylamino)-4-(methylthio)-1-oxobutan-2-ylcarbamate

HRID 1811080Notes

Reaction equation

HRID 1811080 reaction equation
[Br:1][C:2]1[C:3]([CH3:9])=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].[CH2:10]([O:17][C:18]([NH:20][CH:21]([CH2:25][CH2:26][S:27][CH3:28])[C:22](O)=[O:23])=[O:19])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.ON1C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.C(Cl)CCl>C(#N)C.O.C(OCC)(=O)C>[Br:1][C:2]1[C:3]([CH3:9])=[C:4]([NH:5][C:22](=[O:23])[CH:21]([NH:20][C:18](=[O:19])[O:17][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:25][CH2:26][S:27][CH3:28])[CH:6]=[CH:7][CH:8]=1

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 97806N-benzyloxycarbonyl-DL-methionineHCID 1235383-Bromo-o-toluidineHCID 181649HOAt

Product 1

HCID 66606795Racemic benzyl 1-(3-bromo-2-methylphenylamino)-4-(methylthio)-1-oxobutan-2-ylcarbamateYield 69%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

Step 1 A solution of 3-bromo-2-methylaniline (0.662 mL, 5.37 mmol) and racemic 2-(benzyloxycarbonylamino)-4-(methylthio)butanoic acid (1.523 g, 5.37 mmol) in acetonitrile (25 mL) was treated with 1-hydroxy-7-azabenzotriazole (0.878 g, 6.45 mmol), diisopropylethylamine (1.877 mL, 10.75 mmol) and EDC (1.236 g, 6.45 mmol) and stirred at rt. After 20.5 h, the mixture was diluted with water and ethyl acetate. The organic phase was separated, washed with 1 M aqueous HCl and NaHCO3 (aq) and filtered to remove a flocculent white solid. The filtrate was dried and concentrated, and the residue was recrystallized from ethanol to give racemic benzyl 1-(3-bromo-2-methylphenylamino)-4-(methylthio)-1-oxobutan-2-ylcarbamate as a tan solid (1.33 g, 69%). 1H NMR (400 MHz, chloroform-d) δ 8.08 (1H, br. s.), 7.68 (1H, d, J=7.9 Hz), 7.39 (1H, d, J=7.9 Hz), 7.34 (5H, s), 7.04 (1H, t, J=8.0 Hz), 5.58 (1H, d, J=7.9 Hz), 5.14 (2H, s), 4.53 (1H, q, J=7.0 Hz), 2.55-2.72 (2H, m), 2.28 (3H, br. s.), 2.17-2.27 (1H, m), 2.12 (3H, s), 2.01-2.10 (1H, m). Mass spectrum m/z 451, 453 (M+H)+.

Workup

  1. customThe organic phase was separated
  2. washwashed with 1 M aqueous HCl and NaHCO3 (aq)
  3. filtrationfiltered
  4. customto remove a flocculent white solid
  5. customThe filtrate was dried
  6. concentrationconcentrated
  7. customthe residue was recrystallized from ethanol

Sources & evidence

ORD record
ord-822f2ad3b1e745f498d9adae034044fc
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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