Benzeneacetic acid, .alpha.-formyl-, methyl ester → 2-Phenyl-1,3-propanediol

Temperature

4 °C

A one liter three-neck flask fitted with mechanical stirrer, thermometer, nitrogen inlet and addition funnel was charged with water (200 mL), tetrabutylammonium chloride (1.0 g) and 98% sodium borohydride (4.83 g, 0.125 mole). The solution was purged with nitrogen, then stirred and cooled to 4° C. in an ice bath. Crude methyl α-formylphenylacetate (90.6 g, 0.5 mole), prepared according to Example 9, was charged to the addition funnel, and rinsed in with t-butyl methyl ether (25 mL), and added to the above solution at 3°-8° C. The addition took a total of 100 minutes. After 20 minutes into the addition of formylacetate, a second charge of sodium borohydride (4.83 g) was added and rinsed in with water (20 mL). After an additional 1 hour and then again at 1.5 hours, sodium borohydride (4.83 g) in water (20 mL) was added to the batch. The slurry was held at 3° C. for an additional 6 hours, and then allowed to warm to room temperature overnight. The batch was cooled to 15° C., and concentrated hydrochloric acid (46 mL) was added. Methyl isobutyl ketone (MIBK, 100 mL) was added and the batch was stirred vigorously for 15 minutes. The pH of the batch was 1.0. Solid sodium carbonate (45 g) was added and the batch was stirred vigorously for 5 hours. The solids were separated by filtration and washed with MIBK. The solids were dried in vacuo at 65° C. (50.16 g). The aqueous layer from the main filtrate was extracted twice with the MIBK washes. The combined MIBK layers were washed with citric acid solution (10 mL, 5.6 g/15 mL water) and then with saturated sodium chloride solution (20 mL). The solution was filtered through Solka Floc and concentrated in vacuo to 75° C. The pale yellow oil (71.60 g) was crystallized from toluene (80 mL) to give 2-phenyl-1,3-propanediol (53.3 g, 70.05%) m.p. 52°-53.5° C.

1. customA one liter three-neck flask fitted with mechanical stirrer
2. additionthermometer, nitrogen inlet and addition funnel
3. customThe solution was purged with nitrogen
4. additionwas charged to the addition funnel
5. washrinsed in with t-butyl methyl ether (25 mL)
6. additionadded to the above solution at 3°-8° C
7. additionThe addition
8. customa total of 100 minutes
9. additionAfter 20 minutes into the addition of formylacetate
10. additiona second charge of sodium borohydride (4.83 g)
11. additionwas added
12. washrinsed in with water (20 mL)
13. waitagain at 1.5 hours
14. additionsodium borohydride (4.83 g) in water (20 mL) was added to the batch
15. waitThe slurry was held at 3° C. for an additional 6 hours
16. temperatureto warm to room temperature overnight
17. temperatureThe batch was cooled to 15° C.
18. additionconcentrated hydrochloric acid (46 mL) was added
19. additionMethyl isobutyl ketone (MIBK, 100 mL) was added
20. stirringthe batch was stirred vigorously for 15 minutes
21. additionSolid sodium carbonate (45 g) was added
22. stirringthe batch was stirred vigorously for 5 hours
23. customThe solids were separated by filtration
24. washwashed with MIBK
25. customThe solids were dried in vacuo at 65° C. (50.16 g)
26. extractionThe aqueous layer from the main filtrate was extracted twice with the MIBK
27. washThe combined MIBK layers were washed with citric acid solution (10 mL, 5.6 g/15 mL water)
28. filtrationThe solution was filtered through Solka Floc
29. concentrationconcentrated in vacuo to 75° C
30. customThe pale yellow oil (71.60 g) was crystallized from toluene (80 mL)

ORD record

ord-d5fe4058ad02486098e2889e06e867ec

Source dataset

uspto-grants-1993_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05250744