Potassium Iodide → Methyl (2S)-3-(3-bromo-4-iodophenyl)-2-[(tert-butoxycarbonyl)amino]-propanoate

HRID 724657Notes

Reaction equation

HRID 724657 reaction equation
N[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@H:9]([NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:10]([O:12][CH3:13])=[O:11])=[CH:4][C:3]=1[Br:22].N([O-])=O.[Na+].[I-:27].[K+]>Cl.O>[Br:22][C:3]1[CH:4]=[C:5]([CH2:8][C@H:9]([NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C:10]([O:12][CH3:13])=[O:11])[CH:6]=[CH:7][C:2]=1[I:27]

Participants

6

Reactant 3

HCID 4875Potassium IodideHCID 23668193Sodium NitriteHCID 58746653HCID 58746653, compound

Product 1

HCID 11569273Methyl (2S)-3-(3-bromo-4-iodophenyl)-2-[(tert-butoxycarbonyl)amino]-propanoateYield 73%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 962WaterSolvent2×

Conditions

Temperature
40 °C

Procedure

Methyl (2S)-3-(4-amino-3-bromophenyl)-2-[(tert-butoxycarbonyl)amino]-propanoate (19.8 g, 53.0 mmol) suspended in 1 N aqueous hydrogen chloride (500 mL) was treated sequentially at 0° C. with sodium nitrite (3.66 g, 53.0 mmol) in water (75 mL) dropwise. After 15 minutes at 0° C., potassium iodide (8.81 g, 53.1 mmol) in water (75 mL) was added and the solution was heated at 40° C. for 15 minutes. The solution was quenched with saturated aqueous sodium thiosulfate solution (100 mL), and extracted with ethyl acetate (500 mL). The organic phase was washed with 0.1 N Hydrochloric acid solution (500 mL), saturated aqueous sodium bicarbonate solution (500 mL), and dried over sodium sulfate. Purification by silica gel chromatography (10–40% ethyl acetate/hexanes) afforded product as slightly yellow solid (18.7 g, 73%). 1H NMR (400 MHz, CD3OD): δ 7.80 (d, J=8.0 Hz, 1H), 7.55 (d, J=1.8 Hz, 1H), 6.92 (dd, J=8.0, 1.9 Hz), 4.36–4.29 (m, 1H), 3.71 (s, 3H), 3.10–2.79 (m, 1H), 1.37 (s, 9H); LCMS found for C15H19BrINO4Na (M+Na)+: m/z=506.

Workup

  1. customThe solution was quenched with saturated aqueous sodium thiosulfate solution (100 mL)
  2. extractionextracted with ethyl acetate (500 mL)
  3. washThe organic phase was washed with 0.1 N Hydrochloric acid solution (500 mL), saturated aqueous sodium bicarbonate solution (500 mL)
  4. dry with materialdried over sodium sulfate
  5. customPurification by silica gel chromatography (10–40% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-9c1efb37cc324234b9a1f1291622dc64
Source dataset
uspto-grants-2006_11
Patent number
US07141596B2

Reaction notes

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