Ethanolamine → HCID 69516796, Verbindung

Part A. To a slurry of 1-(4-iodo-phenyl)-cyclopropane-carboxylic acid (0.693 g, 2.41 mmol) in CH2Cl2 (3.0 mL) at 0° C. was added (COCl)2 (0.40 mL, 4.6 mmol) dropwise. The reaction was warmed to rt and stirred under N2 for 1 h. The reaction was monitored by LC/MS. Upon completion the reaction was concentrated on the rotary evaporator and diluted with CH2Cl2 (3 mL). Ethanolamine (0.30 mL, 4.54 mmol) was added drop-wise and the reaction stirred for 1.5 h. The reaction was then quenched with H2O and extracted with EtOAc (2×). The organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated to dryness. The crude 1-(4-iodo-phenyl)-cyclopropanecarboxylic acid (2-hydroxy-ethyl)-amide was taken directly to the next reaction without further purification. LC/MS (ESI+) 332.2 (M+H)+, tR=2.16 min (10–90% CH3CN/H2O in a 4-min run). It was dissolved in THF (10.0 mL) and methoxycarbonylsulfamoyl triethylammonium hydroxide inner salt (0.61 g, 2.56 mmol) was added. The reaction was heated to 70° C. for 2 h and then cooled. The reaction mixture was diluted with EtOAc and washed with H2O (2×), brine, dried over Na2SO4, filtered, and concentrated to dryness. The residue was purified by flash chromatography (silica, EtOAc:Hexanes 3:1) to 2-[1-(4-iodo-phenyl)-cyclopropyl]-4,5-dihydro-oxazole (0.41 g, yield: 55%). LC/MS (ESI+) 314.0 (M+H), tR=1.62 min (10–90% CH3CN/H2O in a 4-min run). 1H NMR (CDCl3) δ 7.65 (d, J=8 Hz, 2H), 7.13 (d, J=8.4 Hz, 2H), 4.32 (t, J=9.5 Hz, 2H), 3.87 (t, J=9.1, 9.6, 2H), 1.67 (m, 2H), 1.23 (m, 2H) ppm.

1. concentrationUpon completion the reaction was concentrated on the rotary evaporator
2. additiondiluted with CH2Cl2 (3 mL)
3. stirringthe reaction stirred for 1.5 h
4. customThe reaction was then quenched with H2O
5. extractionextracted with EtOAc (2×)
6. washThe organic layers were washed with brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated to dryness
10. customThe crude 1-(4-iodo-phenyl)-cyclopropanecarboxylic acid (2-hydroxy-ethyl)-amide was taken directly to the next reaction without further purification
11. temperatureThe reaction was heated to 70° C. for 2 h
12. temperaturecooled
13. washwashed with H2O (2×), brine
14. dry with materialdried over Na2SO4
15. filtrationfiltered
16. concentrationconcentrated to dryness

ORD-Eintrag

ord-5e656880afac499bb8203b53cfbb70f4

Quelldatensatz

uspto-grants-2007_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07312214B2