preparation of 1-phenylcyclopropylmethylamine_kain industrial additive

background and overview^[1]

1-phenylcyclopropylmethylamine can be used as a pharmaceutical synthesis intermediate. if 1-phenylcyclopropanemethylamine is inhaled, please move the patient to fresh air; if there is skin contact, take off contaminated clothing, rinse the skin thoroughly with soap and water, and seek medical treatment if you feel uncomfortable; if the eyes are clear in case of contact, separate eyelids, rinse with running water or saline, and seek medical attention immediately; if ingested, rinse mouth immediately, do not induce vomiting, and seek medical attention immediately.

preparation^[1]

the preparation of 1-phenylcyclopropanemethylamine is as follows: add lithium aluminum hydride (23g, 0.35mol, 1.03 equivalent) to 1-phenylcyclopropanenitrile (50g, 0.34mol, 1 equivalent) at 0°c. tetrahydrofuran (500ml, 0.7m) solution. the reaction mixture was stirred at 0°c for 1 hour and then at reflux for 1 hour. the reaction mixture was then cooled and quenched with water (23 ml) and 15% aqueous sodium hydroxide solution (69 ml). the mixture was filtered and concentrated in vacuo to give 1-phenylcyclopropylmethylamine (36 g, 72%). lc-ms: m/z148.1[m+h⁺], retention time = 0.86 minutes; ¹hnmr (400mhz, cdcl₃ )δ7.2-7.4(m, 5h), 2.78(s, 2h), 1.19(brs, 2h), 0.72-0.84(m, 4h).

apply^[1]

1-phenylcyclopropylmethylamine can be used as a pharmaceutical synthesis intermediate. for example, synthesize (2s)-2-[(1r, 2r)-1-methoxy-2-methyl-3-oxo-3-{[(1-phenylcyclopropyl)methyl]amino}propane base]pyrrolidine-1-carboxylic acid tert-butyl ester. from 11 (2.15 g, 7.48 mmol, 1.1 equiv), 1-phenylcyclopropylmethylamine (1.001 g, the crude desired material was synthesized by silica gel chromatography (gradient: 0% to 100), hatu (3.10 g, 8.16 mmol, 1.2 eq) and triethylamine (2.84 ml, 20.4 mmol, 3 eq) % ethyl acetate/heptane) to obtain (2s)-2-[(1r,2r)-1-methoxy-2-methyl-3-oxo-3-{[(1-benzene) as a solid cyclopropyl)methyl]amino}propyl]pyrrolidine-1-carboxylic acid tert-butyl ester (1.93 g, 68%). hplc (protocol a at 45°c): m/z417.3 [m+h+], retention time = 10.575 minutes; 1hnmr (400mhz, dmso-d6), presumably a mixture of rotamers: δ7.75-7.81 (m , 1h), 7.20-7.27(m, 4h), 7.12-7.19(m, 1h), 3.33-3.62 and 3.71-3.80 (br multiplet, 4h in total), 3.28(s, 3h), 2.97-3.17(brm , 2h), 2.14-2.24(m, 1h), 1.67-1.80(brm, 2h), 1.45-1.65(m, 2h), 1.41(s, 9h), 1.00(d, j=6.6hz, 3h), 0.67-0.93 (m, 4h).

main reference materials

[1] cn201280056617.4 cytotoxic peptide and its antibody-drug conjugate