ChemicalBook CAS DataBase List 2-HYDROXYMETHYL-4-BOC-MORPHOLINE

2-HYDROXYMETHYL-4-BOC-MORPHOLINE synthesis

7synthesis methods

Product Name:2-HYDROXYMETHYL-4-BOC-MORPHOLINE
CAS Number:135065-69-9
Molecular formula:C10H19NO4
Molecular Weight:217.26

24424-99-5

40987-24-4

135065-69-9

GENERAL STEPS: Ammonium formate (3.04 g, 48.2 mmol) and 10% palladium/activated charcoal (500 mg) were added to a methanolic solution (50 mL) of (4-benzylmorpholin-2-yl)methanol (1.00 g, 4.82 mmol). The reaction mixture was stirred at room temperature for 4 hours. After completion of the reaction, the mixture was filtered through diatomaceous earth and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in acetonitrile (20 mL) and cooled in an ice bath. To this solution, di-tert-butyl dicarbonate (1.58 g, 7.23 mmol) and triethylamine (1.35 mL, 9.64 mmol) were added sequentially and the reaction mixture was stirred at room temperature for 3 hours. At the end of the reaction, the solvent was evaporated under reduced pressure, water was added to the residue and extracted with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=5:1→1:1) to afford the target compound tert-butyl 2-(hydroxymethyl)morpholine-4-carboxylate (907 mg, 87% yield) as a colorless oil.1H NMR (400 MHz, DMSO-d6) δ 1.40 (9H, s), 2.47-2.66 (1H, m), and 2.73-2.92 (1H, m), 3.25-3.45 (4H, m), 3.70 (1H, d, J=13.4 Hz), 3.79 (1H, dd, J=11.6, 2.4 Hz), 3.85 (1H, d, J=12.8 Hz), 4.77 (1H, t, J=5.5 Hz).

189321-66-2
146 suppliers
$5.00/250mg

135065-69-9
156 suppliers
$8.00/250mg

Yield:135065-69-9 97%

Reaction Conditions:

Stage #1:4-(tert-butoxycarbonyl)morpholine-2-carboxylic acid with borane-THF in tetrahydrofuran at 0 - 20; for 0.416667 h;
Stage #2: with methanol;acetic acid in tetrahydrofuran

Steps:

2.a
A solution of 4-{[(1 ,1-dimethylethyl)oxy]carbonyl}-2-morpholinecarboxylic acid (2.0 g, 21.6 mmol) in THF (45 mL) was cooled to 0 °C. A solution of borane (39 mL, 39.0 mmol, 1 M in THF) was added over 25 min via addition funnel. After warming to RT, the reaction was quenched by dropwise addition of methanol/acetic acid (18 mL, 9:1 v/v). The solvent was removed under reduced pressure and the residue partitioned between ethyl acetate and 1 N HCI. The aqueous layer was extracted with ethyl acetate and combined extracts were washed with water, 1 N NaOH, water, brine and dried over sodium sulfate. Removal of the solvent under reduced pressure afforded 1.83 g (97%) of the desired material. ¹H NMR (400 MHz, CDCI₃) δ ppm 1.49 (s, 9 H) 2.30 (br d, J=11.37 Hz, 1 H) 2.69 - 2.79 (m, J=9.51 , 6.41 , 3.28, 3.28 Hz, 1 H) 2.84 (ddd, J=13.77, 10.86, 3.16 Hz, 2 H) 3.27 - 3.38 (m, 1 H) 3.47 (br s, 1 H) 3.63 - 3.75 (m, 2 H) 4.10 - 4.19 (m, 1 H) 4.27 (br s, 1 H).

References:

SMITHKLINE BEECHAM CORPORATION WO2007/58850, 2007, A2 Location in patent:Page/Page column 43

FullText

24424-99-5 Synthesis

24424-99-5
863 suppliers
$13.50/25G

40987-24-4 Synthesis

40987-24-4
118 suppliers
$32.00/250mg

135065-69-9
156 suppliers
$8.00/250mg

References

24424-99-5 Synthesis

24424-99-5
863 suppliers
$13.50/25G