2-Chloroethanol → 2-{[(4-Methylphenyl)methyl]amino}ethan-1-ol

The procedure of Example 7 was repeated using 2-chloroethanol (20.9 g, 0.26 mol, Kodak), 4-methylbenzylamine (32.7 g, 0.27 mol, Aldrich), water (25 mL) and KOH (14.6 g, 0.26 mol). A white solid was crystallized from the concentrated solution. The crystallized product was collected by suction filtration and recrystallized from hexanes. The filtrate was concentrated under reduced pressure and the residue was fractionally distilled using a 7.5 inch vigreux column. The fraction boiling at 140-1440° C./9 mm pressure was collected. Total yield 15 g (35% yield). 1H NMR (δ, 360 MHz, CDCl3) 2.32 (s, 3H), 2.51 (broad s, 2H), 2.74 (t, 2H), 3.61 (t, 2H), 3.72 (s, 2H) and 7.142 (m, 4H) 13C NMR (δ, 90 MHz, {1H}, CDCl3): 21.0 (—CH3) 50.5 (—NCH2CH2O—), 53.2 (—NCH2CH2O—), 60.7 (—NCH2Ph), 128.1, 129.1 and 143.0 (—CH2Ph). mp 61-62° C. uncorrected. The title compound was also prepared using the following procedure. In a 2L three-neck flask (equipped with a mechanical stirrer and an addition funnel) ethanolamine (91.6 g, 1.5 mol, Aldrich) and 100 mL of toluene were placed. To this solution was added dropwise 4-methylbenzyl chloride (70.3 g, 0.5 mol, Aldrich). The mixture was stirred for 10 hours at room temperature. Crushed KOH (30.0 g, 0.5 mol) was added and stirring was continued for another 3 hours. Water (300 mL) was added to dissolve all solid. The mixture was poured into a separatory funnel and the toluene layer was separated. The aqueous layer was extracted with 50 mL portions of methylene chloride three times. The combined extracts were dried on anhydrous sodium sulfate and rotovaped to remove the solvents. A white solid was crystallized from the concentrated solution. The crystallized product (34 g) was collected by suction filtration and washed with several mL of toluene. The filtrate was concentrated under reduced pressure and the residue was fractionally distilled using a 7.5 inch vigreux column. The fraction boiling at 140-144° C./9 mm pressure was collected. Total yield isolated 46.5 g (57% yield).

1. customA white solid was crystallized from the concentrated solution
2. filtrationThe crystallized product was collected by suction filtration
3. customrecrystallized from hexanes
4. concentrationThe filtrate was concentrated under reduced pressure
5. distillationthe residue was fractionally distilled
6. customThe fraction boiling at 140-1440° C./9 mm pressure was collected
7. customThe title compound was also prepared
8. stirringstirring
9. waitwas continued for another 3 hours
10. dissolutionto dissolve all solid
11. additionThe mixture was poured into a separatory funnel
12. customthe toluene layer was separated
13. extractionThe aqueous layer was extracted with 50 mL portions of methylene chloride three times
14. dry with materialThe combined extracts were dried on anhydrous sodium sulfate
15. customto remove the solvents
16. customA white solid was crystallized from the concentrated solution
17. filtrationThe crystallized product (34 g) was collected by suction filtration
18. washwashed with several mL of toluene
19. concentrationThe filtrate was concentrated under reduced pressure
20. distillationthe residue was fractionally distilled
21. customThe fraction boiling at 140-144° C./9 mm pressure was collected
22. customTotal yield
23. customisolated 46.5 g (57% yield)

ORD record

ord-9ff53bc7ed18499eb9cc233a0da57359

Source dataset

uspto-grants-2001_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06288224B1