References
- Collet , J. J. and Wilen , S. H. 1981 . “Enantiomers, Racemates, and Resolutions” , 257 New York, NY : J. Wiley & Sons, Inc. .
- e.g. 20% THF-hexane, RF = 0.52 and 0.49 for 2a
- 5% MeOH-CH2Cl2 RF = 0.34 for 3a(SS) and RF = 0.17 for 3a(SR)
- 5% MEOH-CH2Cl2 RF = 0.54 and 0.45 for L-phenylalanine derivatives of la
- Chiralpak AD: Amylose-tris[3,5-dimethyl phenyl carbamate] coated on silica gel. Chiralpak AS: Amylose-tris[(S)-α-methyl benzyl carbamate] coated on silica gel
- X-ray Crystallography was performed by Dr. Cynthia Day, Crystalytic Company, P. O. Box 82286, Lincoln, NE 68501, on the ditosylate salt of 1a,(+)-S
- The amines were prepared by the addition of cyclohexylmethyl-Magesiumbromide to cyanopyridine7b to give the ketimine intermediate. This was followed by in situ reduction with NaBH4-methanol. b). P. L. Pickard and T. L. Tolbert, J. Org. Chem., 93, 4886 (1961). R. L. Frank and C. Weatherbee, J. Am. Chem. Soc., 70, 3482 (1948)
- Windridge , G. C. and Jorgensen , E. C. 1971 . ibid. , 93 : 6318
- Compound 2a: 1H NMR (250 MHz) (CDCl3): 6 0.85 (d. 3H, CH3), 0.95 (d, 3H, CH3), 0.95–1.15 (m, 6H, 6ax.cycl), 1.4 (s, 9H, tBu), 1.65 (m, 7H, 5eq.cyc1, CH2), 2.1 (m, 1H, CHMe 2), 3.95 (m, 1H, CHCO), 5.1 (m, 2H, CH, NH), 6.8 (m, 1H, NH), 7.18 (m, 2H, pyr), 7.6 (m, 1H, pyr). 8.5 (m, 1H, pyr). Compound 3a(SS): 1H NMR (CDCl3): δ 0.85 (d, 3H, CH3), 0.95 (d, 3H, C4). 0.9–1.15 (m, 6H, 6ax.Cycl) 1.4 (br, 2H, NH2), 1.7 (m, 7H, 5eq, CH2), 2.3 (m, 1H, CHMe2), 3.2 (d, 1H, CHCO), 5.15 (dd, 1H, CH), 7.15 (m, 1H, pyr), 7.2 (d, 1H, pyr), 7.60 (m, 1H, pyr). 7.95 (br, 1H, NH), 8.55 (d,1H, pyr). Compound 3a(SR): 1H NMR (CDCl3): δ 0.7 (d, 3H, CH3), 0.92 (d, 3H, CH3), 0.9–1.15 (m, 6H, 6ax.Cycl), 1.5 (s, 2H, NH2), 1.65 (m, 7H, 5eq, CH2), 2.2 (m, 1H, CHMe2), 3.2 (d, 1H, CHCO), 5.15 (dd, 1H, CH), 7.1 (m, 1H, pyr), 7.2 (m, 1H, pyr), 7.6 (m, 1H, pyr), 7.8 (br, 1H, NH), 8.55 (m, 1H, pyr). Compound 1a,(+)-S: 1H NMR (CDCl3): δ 0.95 (m, 3H, 3ax.cycl), 1.5–1.7 (m, 7H, 5eq.cyc1, CH2), 1.72 (br, 2H, NH2), 4.05 (m, 1H, CH), 7.15 (m, 1H, pyr). 7.25 (m, 1H, pyr), 7.6 (t, 1H, pyr) 8.55 (m, 1H, pyr). Compound 1a,(-)-R: Identical NMR spectrum as 1a(S). Data for the 3-pyridyl derivatives: 2b, 3b(SS) 3b(SR), and 1b(S) 1b(R)
- 3a(SS) does not crystallize as a dihydrochloride, and 3a(SR) does not crystallize as the ditosylate
- It was slightly less pure chemically, 97% by HPLC, because of incomplete hydrolysis