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

HRID 724668Notes

Reaction equation

HRID 724668 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[Cl:22].N([O-])=O.[Na+].[I-:27].[K+]>Cl.O.C(OCC)(=O)C>[C:18]([O:17][C:15]([NH:14][C@@H:9]([CH2:8][C:5]1[CH:6]=[CH:7][C:2]([I:27])=[C:3]([Cl:22])[CH:4]=1)[C:10]([O:12][CH3:13])=[O:11])=[O:16])([CH3:21])([CH3:20])[CH3:19]

Participants

7

Reactant 3

HCID 4875Potassium IodideHCID 23668193Sodium NitriteHCID 58746521Methyl (2S)-3-(4-amino-3-chlorophenyl)-2-[(tert-butoxycarbonyl)amino]propanoate

Product 1

HCID 11546659Methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-(3-chloro-4-iodophenyl)propanoateYield 53%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Methyl (2S)-3-(4-amino-3-chlorophenyl)-2-[(tert-butoxycarbonyl)amino]propanoate (3.00 g, 9.12 mmol) in aqueous hydrochloric acid solution (1.0 N, 100.0 mL) at 0° C. was treated with a solution of sodium nitrite (692 mg, 10.0 mmol) in water (10 mL). The solution was stirred at 0° C. for 30 minutes. A solution of potassium iodide (1.89 g, 11.4 mmol) in water (10 mL) was added and the solution stirred 30 minutes at rt and then 10 minutes at 35° C. The solution was diluted with ethyl acetate (200 mL), quenched with aqueous sodium thiosulfate solution (1.0 N, 500 mL), and the organic phase separated. The organic layer was washed with aqueous hydrochloric acid solution (1.0 N, 100 mL), brine (100 mL), and after drying over sodium sulfate was concentrated in vacuo. Purification by silica gel chromatography (10–40% ethyl acetate/hexanes) afforded product as a yellow solid (2.1 g, 53%). 1H NMR (400 MHz, CD3OD): δ 7.80 (d, J=8.0 Hz, 1H), 7.37 (s, 1H), 6.90 (d, J=8.2 Hz, 1H), 4.36–4.33 (m, 1H), 3.70 (s, 3H), 3.12–3.07 (m, 1H), 2.86–2.80 (m, 1H), 1.37 (s, 9H); LCMS found for C10H12ClINO2 (M+H)+: m/z=340.

Workup

  1. stirringthe solution stirred 30 minutes at rt
  2. custom10 minutes
  3. customat 35° C
  4. customquenched with aqueous sodium thiosulfate solution (1.0 N, 500 mL)
  5. customthe organic phase separated
  6. washThe organic layer was washed with aqueous hydrochloric acid solution (1.0 N, 100 mL), brine (100 mL)
  7. dry with materialafter drying over sodium sulfate
  8. concentrationwas concentrated in vacuo
  9. customPurification by silica gel chromatography (10–40% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-5d3aad5b67594825abd17a98f15220f9
Source dataset
uspto-grants-2006_11
Patent number
US07141596B2

Reaction notes

Loading…