TERT-BUTYL CIS-(4-HYDROXYMETHYL)CYCLOHEXYLCARBAMATE

Synthesis

General procedure for the synthesis of cis-1-(Boc-amino)-4-(hydroxymethyl)cyclohexane from di-tert-butyl dicarbonate and (1r,4r)-4-aminocyclohexanemethanol: Di-tert-butyl dicarbonate (3.04 g, 13.9 mmol) was slowly added to (1r,4r)-4-aminocyclohexanemethanol (1.50 g, 11.6 mmol) in a room temperature tetrahydrofuran (20 mL) in a stirred solution. The reaction mixture was stirred overnight at room temperature. Subsequently, the solvent was removed by rotary evaporation and the residue was partitioned between ethyl acetate and water. The organic phase was separated, washed sequentially with water and saturated saline, dried over anhydrous magnesium sulfate, and the solvent was again removed by rotary evaporation. The resulting residue was treated with hexane and the suspension formed was filtered to give cis-1-(Boc-amino)-4-(hydroxymethyl)cyclohexane as a white solid (2.11 g, 79% yield). The product was detected by low resolution mass spectrometry (LRMS) and showed m/z of 228 (M-H)+.1H NMR (DMSO-d6) δ: 0.84-0.95 (m, 2H), 1.05-1.18 (m, 2H), 1.20-1.29 (m, 2H), 1.40 (s, 9H), 1.71-1.80 (m, 3H), 3.14 (m , 1H), 3.21 (t, 2H), 4.41 (t, 1H), 6.73 (d, 1H).

References

[1] Patent: EP2554544, 2013, A1. Location in patent: Paragraph 0161
[2] Journal of Labelled Compounds and Radiopharmaceuticals, 1999, vol. 42, # SUPPL. 1, p. S309-S310,S311
[3] Journal of Labelled Compounds and Radiopharmaceuticals, 1999, vol. 42, # 3, p. 293 - 307
[4] Patent: US2015/31674, 2015, A1. Location in patent: Paragraph 0274