反应详情

温度

28 °C

To a 780 L Hastelloy reactor, compound C (33 kg, 1.0 eq.), 5% platinum carbon (sulfided, 0.33 kg, 0.010 parts) and dichloromethane (578 kg, 17.5 parts) were charged. Agitation was started and reactor contents were adjusted to 22° C. (19-25° C.). The reactor was pressurized with ca. 30 psi hydrogen and the reaction mixture gently heated to 28° C. (25-31° C.). Hydrogenation of the reactor contents was performed under ca. 30 psi at 28° C. (25 to 31° C.; maximum 31° C.) until the reaction was complete by HPLC. After 16.5 hrs, the reaction was deemed complete after confirming the disappearance of starting material (0.472 A %). The contents of the reactor were circulated through a conditioned celite pad (0.2-0.5 kg celite conditioned with 20-55 kg dichloromethane) prepared in a 8″ sparkler filter to remove the platinum catalyst. The reactor and celite bed were rinsed forward with two portions of dichloromethane (83 kg, 2.5 parts each). The filtrate was transferred to and concentrated in a 570 L GLMS reactor under a atmospheric pressure to ca. 132 L (4 parts volume). Ethanol (69 kg, 2.1 parts) was charged and concentration continued under atmospheric pressure to ca. 99 L (3 parts volume). In-process NMR indicated that the dichloromethane content was 39%. Ethanol (69 kg, 2.1 parts) was charged again and concentration continued again to ca. 99 L (3 parts volume). In-process NMR indicated that the dichloromethane content was 5%. The reaction mixture was then adjusted to 3° C. (0 to 6° C.), agitated for ca. 1 hr, and the resulting slurry filtered onto a jacketed pressure nutsche fitted with a filter cloth. The reactor, pump, and lines were rinsed forward with cold [3° C. (0-6° C.)]ethanol (26 kg, 0.8 parts). The wet filter cake (36.6 kg) was dried under vacuum at 40-50° C. with a maximum temperature of water bath (to heat dryer jacket) of 50° C. LOD analysis after 12.5 hrs indicated solvent content was at 0.1%. The dry product (D) was discharged (26.4 kg) in 89.5% yield. HPLC showed 98.4 A % purity, with dechlorinated impurity at 0.083%.

1. customreactor contents were adjusted to 22° C.
2. custom(19-25° C.)
3. customwas performed under ca. 30 psi at 28° C.
4. custom(25 to 31° C.; maximum 31° C.)
5. customprepared in a 8″ sparkler
6. filtrationfilter
7. customto remove the platinum catalyst
8. washThe reactor and celite bed were rinsed forward with two portions of dichloromethane (83 kg, 2.5 parts each)
9. concentrationconcentrated in a 570 L GLMS reactor under a atmospheric pressure to ca. 132 L (4 parts volume)
10. additionEthanol (69 kg, 2.1 parts) was charged
11. concentrationconcentration
12. additionEthanol (69 kg, 2.1 parts) was charged again
13. concentrationconcentration
14. customwas then adjusted to 3° C.
15. custom(0 to 6° C.)
16. filtrationthe resulting slurry filtered onto a jacketed pressure nutsche
17. customfitted with a filter cloth
18. washThe reactor, pump, and lines were rinsed forward with cold [3° C. (0-6° C.)]ethanol (26 kg, 0.8 parts)
19. customThe wet filter cake (36.6 kg) was dried under vacuum at 40-50° C. with a maximum temperature of water bath
20. temperature(to heat dryer jacket) of 50° C
21. waitLOD analysis after 12.5 hrs indicated