Potassium Iodide → HCID 86609571, compound

HRID 2114747Notes

Reaction equation

HRID 2114747 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:7]([O:9][C:10](=[O:21])[C@H:11]([NH2:20])[CH2:12][CH2:13][CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH3:8].[I-].[K+].[CH3:24][O:25][C:26](=[O:34])[CH2:27][CH2:28][CH2:29][S:30][CH2:31][CH2:32]Cl.C([O-])(O)=O.[Na+]>CN(C=O)C.O>[CH2:7]([O:9][C:10](=[O:21])[C@H:11]([NH:20][CH2:32][CH2:31][S:30][CH2:29][CH2:28][CH2:27][C:26]([O:25][CH3:24])=[O:34])[CH2:12][CH2:13][CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH3:8]

Participants

8

Reactant 5

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 22592554Methyl 4-[(2-chloroethyl)thio]butanoateHCID 86609572HCID 86609572, compound

Product 1

HCID 86609571HCID 86609571, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent3×HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
90 °C

Procedure

A mixture of cesium carbonate (2.71 g, 8.32 mmol) and DMF and water (10:1, 20 mL) was stirred at room temperature for 30 min before a solution of (R)-2-aminohexanedioic acid diethyl ester (prepared from D-α-aminoadipic acid according to Huang, et al., Synth. Commun. 1989, 19, 3485-3496, 1.80 g, 8.28 mmol) in DMF and water (10:1, 2 mL) was added via cannula. After 30 min at room temperature, potassium iodide (276 mg, 1.66 mmol) followed by 4-(2-chloroethylsulfanyl)-butyric acid methyl ester (prepared according to PCT 03/007941, 1.63 g, 8.29 mmol) in DMF and water (10:1, 5 mL) were added. After 23 h at room temperature, the reaction mixture was heated at 90° C. After 2.5 h at 90 ° C, the reaction was cooled to room temperature and saturated aqueous NaHCO3 (100 mL) was added. The mixture was extracted with EtOAc (3×75 mL) and the combined extracts were washed with water (2×100 mL) and brine (2×100 mL) then dried (Na2SO4) filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (10%→40% EtOAc/hexane, gradient) two times afforded 893 mg (29%) of (R)-2-[2-(3-methoxycarbonyl-propylsulfanyl)-ethylamino]-hexanedioic acid diethyl ester.

Workup

  1. additionwas added via cannula
  2. additionwere added
  3. waitAfter 23 h at room temperature
  4. waitAfter 2.5 h at 90 ° C
  5. temperaturethe reaction was cooled to room temperature
  6. extractionThe mixture was extracted with EtOAc (3×75 mL)
  7. washthe combined extracts were washed with water (2×100 mL) and brine (2×100 mL)
  8. dry with materialthen dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customPurification of the residue by flash column chromatography on silica gel (10%→40% EtOAc/hexane, gradient) two times

Sources & evidence

ORD record
ord-0f3cc1c6a8384a1ca0e25250a99a741f
Source dataset
uspto-grants-2008_10
Patent number
US07435746B2

Reaction notes

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