As the paragraph descriping shows that 1001180-21-7 is playing an increasingly important role.
1001180-21-7, (R)-tert-Butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate is a piperazines compound, ?involved in a variety of chemical synthesis. Rlated chemical reaction is continuously updated
1001180-21-7, A 3000 L glass-lined reactor was evacuated and filled with nitrogen to normal pressure 3 times. Water (660.0 kg) was added into the reactor while maintaining the temperature in the range of 20-30 C. The stirrer was started, followed by the addition of potassium dihydrogen phosphate (9.2 kg), dipotassium phosphate (23.7 kg) and glucose (78.5 kg). The mixture was stirred until solid dissolved completely. Then 30.1 kg of this buffer mixture was discharged into a 50 L drum for future use. To the reactor was added (R)-tert-butyl 4-(5-methyl-7-oxo-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (66.0 kg) and PEG400 (732.6 kg) and the mixture was heated to about 30-35 C. Maintaining the temperature at 30-35 C., a mixture of buffer solution (20.0 kg), KRED-101 (2.4 kg), GDH (3.4 kg) and NADP (2.2 kg) was added into the mixture. The mixture was then maintained at 32-37 C. for reaction while controlling the pH at 6.8-7.1. After about 6 h, the mixture was monitored by TLC and HPLC until ketone starting substrate was ?1.0%. During the reaction, potassium hydroxide solution (total 46.2 kg) and extra enzyme buffer solution prepared with purified water (5.0 kg), KRED-101 (0.24 kg), GDH (0.34 kg) and NADP (0.22 kg) were added. To a glass-lined reactor, isopropyl acetate (1148.6 kg) was added. The reaction mixture from the previous paragraph was added to the reactor in three portions. Each time, it was stirred for 15-20 min and held for at least 0.5 h before separation at 20-30 C. This extraction process was repeated three times. The organic phases were combined. At 20-30 C., the combined organic phases were washed with purified water (329.3 kg). It was stirred for 25-30 min and held for at least 30 min before separation. The organic phase was left in the reactor and the washing process was repeated. The organic phase was decolorized with active carbon (6.6 kg) and stirred for 1-1.5 h. The mixture was filtered via a Nutsche filter. The cake was washed with isopropyl acetate (57.5 kg). The filtrates were combined. The filtrate was then transferred into a thin film evaporator and concentrated at ?55 C. under reduced pressure until 500-600 L remained. The concentrated mixture was filtered and transferred into a glass-lined reactor, then concentrated at ?55 C. under reduced pressure until 50-60 L remained. The mixture was then heated to 50-55 C. and stirred at this temperature for 0.5-1.5 h under nitrogen. n-Heptane (277.2 kg) was added into the mixture at the rate of 20-30 kg/h while maintaining the temperature at 50-55 C. The mixture was then cooled to 20-30 C. at the rate of 5-10 C./h. The mixture was stirred at 20-30 C. for 1 h, then heated to 50-55 C. and stirrer for 1-2 h, and then cooled to 15-20 C. at a rate of 5-10 C./h for crystallization. It was sampled to be analyzed by HPLC every 1-2 h until wt % of the mother liquid was ?3% or the change of the wt % between consecutive samples was ?0.5%. The mixture was then filtered with a centrifuge. The filter cake was washed with n-heptane (45.0 kg). The filtrate was transferred into a glass-lined reactor and concentrated at ?45 C. under reduced pressure (?-0.06 MPa) until no more distillate was observed (approximately 20 L remained). Isopropyl acetate (20.0 kg) was added, the mixture was heated to 45-55 C. and stirred for 0.5-1 h. The mixture was dried at 40-50 C. to give tert-butyl 4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate as grey solid (50.65 kg, 76.3% yield), HPLC rt=18.93 min, 99.9% pure, 100% de, 100% ee. The HPLC conditions are given in Table 1 below.
As the paragraph descriping shows that 1001180-21-7 is playing an increasingly important role.
Reference£º
Patent; Genetech, Inc.; Babu, Srinivasan; Gosselin, Francis; Ran, Yingqing; Remarchuk, Travis; Savage, Scott J.; Stults, Jeffrey; Yajima, Herbert; US2015/99880; (2015); A1;,
Piperazine – Wikipedia
Piperazines – an overview | ScienceDirect Topics