Benzyl Alcohol → HCID 11150217, compound

Temperature

20 °C

To 68.3 g of methyl N-benzylazetidine-2-carboxylate (see Example 4 above; purity 89.8 area % ), acetonitrile (127 mL), K2CO3(s) (23.3 g) and benzyl alcohol (75.6 g) were added. The stirred reaction slurry was heated to between 75 and 80° C., and a modest vacuum (p>700 mbar) was applied. Methanol and acetonitrile were distilled off and, as the reaction slurry became highly concentrated, more acetonitrile was added and the distillation was continued. This procedure was repeated until a conversion of 97% was attained. The concentrated reaction mixture was cooled to 20° C. and diluted with acetonitrile (70 mL). The solid salts were filtered off and the filter cake was washed with acetonitrile (3×50 mL). The solvent was evaporated off at 40° C. To the remaining high-boiling liquid, heptane (1.5 L) and 5% (w/w) NaCl(aq.) (700 mL) were added, giving a mixture of three phases. 2 M H2SO4 (5 mL) was added to give a pH of about 8. After two more extractions of the organic phase with 5% (w/w) NaCl (aq), and water at pH 8, almost all of the third phase (benzyl alcohol) was successfully dissolved. Water (550 mL) was added to the organic phase and the pH was adjusted to 2.6 with 2M H2SO4 (38 mL). After separation, the organic phase was extracted with two more portions of acidified water (150 mL H2O at pH 2.2, followed by 50 mL H2O at pH 2.6). The organic phase was discarded. To the combined aqueous phases (pH 2.5), heptane (1.25 L) was added and pH was adjusted to 4.5 with K2CO3(s). The organic phase was separated off and washed with 10% (w/w) NaCl (aq.) and water. The obtained organic phase was evaporated at 40° C., until a bright yellow to brownish liquid remained (65.1 g, according to titration 94.0% (w/w) product, 4.3% (w/w) benzyl alcohol, purity(GC) 99.5 area % ). A second crop of product was isolated as above by extracting the remaining water phase (pH 4.5) with three more portions of heptane (0.25/0.1/0.1 L heptane at pH 5.8/5.2/4.9). Yield 7.8 g of a slightly more coloured product (assay 90% (w/w) according to titr., purity(GC) 97.9 area %), resulting in a total yield of 87% (68.2 g, 0.242 mol).

1. customThe stirred reaction slurry
2. temperaturewas heated to between 75 and 80° C.
3. distillationMethanol and acetonitrile were distilled off and, as the reaction slurry
4. concentrationbecame highly concentrated
5. additionmore acetonitrile was added
6. distillationthe distillation
7. customThe concentrated reaction mixture
8. filtrationThe solid salts were filtered off
9. washthe filter cake was washed with acetonitrile (3×50 mL)
10. customThe solvent was evaporated off at 40° C
11. additionTo the remaining high-boiling liquid, heptane (1.5 L) and 5% (w/w) NaCl(aq.) (700 mL) were added
12. customgiving
13. additiona mixture of three phases
14. customto give a pH of about 8
15. extractionAfter two more extractions of the organic phase with 5% (w/w) NaCl (aq), and water at pH 8
16. dissolutionalmost all of the third phase (benzyl alcohol) was successfully dissolved
17. additionWater (550 mL) was added to the organic phase
18. customAfter separation
19. extractionthe organic phase was extracted with two more portions of acidified water (150 mL H2O at pH 2.2, followed by 50 mL H2O at pH 2.6)
20. additionTo the combined aqueous phases (pH 2.5), heptane (1.25 L) was added
21. customThe organic phase was separated off
22. washwashed with 10% (w/w) NaCl (aq.) and water
23. customThe obtained organic phase was evaporated at 40° C.
24. customA second crop of product was isolated as above
25. extractionby extracting the remaining water phase (pH 4.5) with three more portions of heptane (0.25/0.1/0.1 L heptane at pH 5.8/5.2/4.9)
26. customYield 7.8 g of a slightly more coloured product (assay 90% (w/w) according to titr., purity(GC) 97.9 area %), resulting in a total yield of 87% (68.2 g, 0.242 mol)

ORD record

ord-649aaeb2c32c40f984aed8af4d2907a9

Source dataset

uspto-grants-2003_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06506907B1