(αS)-α-(2-Methylpropyl)-2-(1-piperidinyl)benzenemethanamine

The preparation of 2-methyl-1-propene Grignard reagent lithium chloride is described in Angew. Chem. Int. Ed. 2004, 43, 3333. Under the protection of nitrogen, compound 112.2g (0.38mol, 1eq) was dissolved in 336 g of tetrahydrofuran, and the temperature was lowered to below -20 deg. C. A solution of 2-methyl-1-propenylmagnesium chloride lithium choride in tetrahydrofuran solution (638mL, 3eq, 1.8 mol / L) was added dropwise, temperature was maintained such that it does not exceed -5 deg. C, and stirred at room temperature for 1 h. The completion of the reaction was monitored by HPLC. The S/R ratio of the two isomers in the chiral HPLC was 98.2/1.8. 10% hydrochloric acid was added at 0-10C to adjust pH = 1-2, and stirred for 1 hour at room temperature. After the completion of deprotection was detected by HPLC, the mixture was extracted once with 100 g methyl t-butyl ether. The aqueous layer was adjusted to pH 8 with 20% NaOH, the organic layers were combined, 1.2 g of 10% palladium on carbon was added and reduction was carried out using 1 atm of hydrogen gas. After completion of the reaction, the catalyst was filtered off, the solvent was evaporated to dryness under reduced pressure and the product was distilled under reduced pressure to give 70.3g, HPLC: 99.1%, 99.3 % ee, 74.6% yield.Under nitrogen protection, compound 3 70.6 g (0.287mol, 1eq), benzyl 4-carboxymethyl-2-ethoxybenzoate 90.4 g (0.287mol, 1eq), tetramethoxysilane 131.0 g (0.861mol, 3eq ) and 285g of toluene were added, and heated to reflux for 10 hours. The control of starting material in HPLC was completed, cooled, concentrated under reduced pressure and recrystallized from ethanol / methyl tert-butyl ether to give an off-white solid 123.6g, HPLC 99.0%, yield 79.4%, 99.4% ee.Under nitrogen protection, compound 360.2 g (0.245 mol, 1 eq), methyl 4-carboxymethyl-2-ethoxybenzoate 58.5 g (0.245 mol, 1 eq), tris(2, 2, 2-trifluoroethyl)borate 226.3 g (0.735 mol, 3 eq) and toluene 240 g were added and heated to reflux for 16 hours. The control of the raw materials in the HPLC was completed, cooled, concentrated under reduced pressure, and recrystallized from ethanol/methyl tert-butyl ether to give 103.6 g of a white solid.HPLC 99.1%, yield 90.7%, 99.2% ee.

Molecular Weight:246.39
XLogP3:3.5
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:4
Exact Mass:246.209598838
Monoisotopic Mass:246.209598838
Topological Polar Surface Area:29.3
Heavy Atom Count:18
Complexity:233
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes