4-Morpholineethanol

CLEAR COLOURLESS TO YELLOW LIQUID

Liquid

2-(morpholin-4-yl)ethanol is a primary alcohol that is ethanol in which one of the methyl hydrogens is replaced by a morpholin-4-yl group. It is a primary alcohol, a tertiary amino compound and a member of morpholines.

A mixture of 2-bromoethanol (27.9 g, 223 mmol), morpholine (40 g, 459 mmol) and K2C03 (48.4 g, 350 mmol) in CH3CN (30 mL) was refluxed for 3 h. The mixture was then cooled to rt and filtered. The filtrate was concentrated in vacuo to give the title compound as a yellow solid (24.40 g, 83percent), which was used for next step without further purification.A mixture of 2-bromoethanol (27.9 g, 223 mmol), morpholine (40 g, 459 mmol) and In a 500 mL round-bottomed flask, 2-bromoethanol (27.9 g, 223 mmol), morpholine (40 g, 459 mmol), K2CO3 (48.4 g, 350 mmol), and CH3CN (30 mL) were added and refluxed for 3 h. The reaction was completed.The reaction was cooled to room temperature, filtered and the solvent evaporated to dryness. The crude product was used in the next reaction without further treatment to give a yellow solid (24.40 g, 83percent).Morpholine (5ml, 57 mmol) was dissolved in acetonitrile (20ml) and 3-bromopropanol (5.7 mL, 63 mmol) was added slowly and the mixture was refluxed for 3h. Yield 65percent. HPLC purity: 98.7percent.To a stirred solution of morpholine (2 g, 22.9 mmol, Spectrochem) in dry tetrahydrofuran (20 mL) was added potassium carbonate (6.3 g, 45.9 mmol, Ranchem) and 2- bromoethanol (2.4 mL, 34.4 mmol) and heated to 75 00 for 3 h. Reaction completion was monitored by TLC. The reaction mixture was concentrated under reduced pressure and water (20 mL) was added and extracted in ethyl acetate (3 x 50 mL). Combinedextract was washed with water, brine solution and dried over anhydrous Na2SO4.The crude product was isolated as brown liquid and was used for next step without further purification (2 g, 65percent). 1H NMR (400 MHz, DMSO-d6): 6 4.40 (s, 1 H), 3.64-3.54 (m, 6H), 2.48-2.33 (m, 6H). LCMS: (Method A) 132 (M-f-H), Rt. 1.2 mm, 99.6percent (Max)To a stirred solution of 2-bromoethan-l-ol (11.78 mL, 165.92 mmol, 7.0 eq) in acetonitrile (68 ml) was added potassium carbonate (9.8 g, 71.10 mmol, 3.0 eq). The reaction mixture was stirred for about 30 minutes at room temperature then added morpholine (3.2 g, 23.70 mmol, 1.0 eq). The reaction mixture was refluxed for overnight. TLC indicated starting material was consumed and the desired product was observed. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated to get crude residue which was purified by column chromatography by using 3percent MeOH in DCM as an eluent to afford the desired compound (2.5 g, yield: 60.0percent) as a brown colour liquid. 1H NMR (DMSO-dTo a stirred solution of 2-bromoethan-1-ol ( 43.0 g, 344.35 mmol, 6.0 eq) inacetonitrile (75 mL) was added cesium carbonate (56.0 g, 172.17 mmol, 3.0 eq). The reactionmixture was stirred at room temperature for 1 hour, then added morpholine (5.0 g, 57.392mmol, 1.0 eq). The reaction mixture was refluxed for overnight. After completion of thereaction (monitored by TLC), the reaction mixture was allowed to cool to room temperature, 10 filtered through celite pad and the filtrate was concentrated under reduced pressure. Theresidue was purified by silica gel column chromatography by using 3-10percent methanol in DCMgradient. The fractions containing the expected product were combined and concentratedunder reduced pressure to obtain the title compound (3 .0 g, yield: 39.89percent) as a colourless oil.1H NMR (300 MHz, CDCb): 8 ppm 3.72 (t, J = 4.8 Hz, 4H), 3.63 (t, J = 5.1 Hz, 2H), 2.58-15 2.49 (m, 6H).

4-(2-Hydroxyethyl)morpholine is a morphiline derivative used in the preparation of ester prodrugs of naproxen. 4-(2-Hydroxyethyl)morpholine was also shown to induce repair in rat hepatocyte primary cu lture/DNA.

Intermediates

Molecular Weight:131.17
XLogP3:-0.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:131.094628657
Monoisotopic Mass:131.094628657
Topological Polar Surface Area:32.7
Heavy Atom Count:9
Complexity:71.5
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes