Phenylmethyl (3S)-3-methyl-1-piperazinecarboxylate

A 1-liter four-neck flask with a thermometer, condenser and stirrer was charged with 100.2 g (= 1. 00 mole) of 2-methylpiperazine provided as a racemic modification, 90.0 g (= 0.600 mole) of D-tartaric acid, 170 g of water and 36.0 g (= 0.600 mole) of acetic acid, being followed by heating up to 72°C and aging at the temperature for 2 hours. The amount of the solvent based on the amount of racemic 2-methylpiperazine was 1.69 times by weight. Then, cooling was carried out down to 15°C, taking 12 hours, and precipitated crystals were collected by filtration. The obtained crystals were dried in vacuum, to obtain 114.0 g (= 0.456 mole) of a diastereomer salt. The optical purity of the salt was 93.25percent ee, and the S-isomer yield in the obtained salt based on the amount of the S-isomer in the 2-methylpiperazine supplied as a racemic modification was 88.0percent. Then, a 500 ml flask was charged with 190 g of water, and 114.0 g of the obtained crystals {pure (S)-2-methylpiperazien content = 44.0 g} were added. Perfect dissolution was achieved at 80 to 85°C, being followed by cooling down to 15°C, taking 5 hours. Precipitated crystals were collected by filtration and dried in vacuum, to obtain 100.5 g of a salt. Its optical purity was 99.5percent ee, and the S-isomer yield in the obtained salt based on the amount of the (S)-2-methylpiperazine in the supplied crystals was 91.1percent. A 200 ml four-neck flask with a thermometer, condenser and stirrer was charged with 75 g of water, and 25.1 g of (S)-2-methylpiperazine D-tartaric acid salt (= 0.100 mole, optical purity of 2-methylpiperazine = 99.5percent ee) and 7.8 g (= 0.100 mole) of 95percent pure calcium hydroxide were added. The slurry was heated up to 70 to 80°C, and stirred for 3 hours, then being cooled to room temperature. Then, the non-dissolved solvent was filtered away to obtain the mother liquor. The mother liquor was GC-analyzed, and as a result, it was found that 9.2 g (= 0.0918 mole) of 2-methylpiperazine existed in the mother liquor (yield 91.8percent). Furthermore, from the result of HPLC analysis, the optical purity of (S)-2-methylpiperazine was 99.5percent ee. Subsequently concentration was carried out down to a water content of about 50 wtpercent, and 1-butanol was added. Then, azeotropic dehydration was carried out till the water content of the system became less than 1 wtpercent, and distillation under reduced pressure was carried out to isolate (S)-2-methylpiperazine. The optically active (S)-2-methylpiperazine (optical purity 99.5percent ee) obtained as described above was used to perform a reaction in quite the same way as the method of Example 1. Stirring was carried out for 2 hours at 0 to 5°C, being followed by stirring at room temperature for 12 hours. The reaction solution was analyzed, and as a result, the reaction yield of 1-benzyloxycarbonyl-3-methylpiperazine was 84.6percent (based on the amount of 2-methylpiperazine), and its optical purity was 99.5percent ee, showing no decline of optical purity.

Molecular Weight:234.29
XLogP3:1.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:234.136827821
Monoisotopic Mass:234.136827821
Topological Polar Surface Area:41.6
Heavy Atom Count:17
Complexity:252
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes