Reaction Steps
A solution of 4,4-dimethyl-heptanoic acid (1.58 g, 10 mmol) and triethylamine (4.6 mL) in 50 mL THF was cooled to 0° C. and treated with 2,2-dimethyl-propionyl chloride (1.36 mL). After one hour, 4R-methyl-5S-phenyl-oxazolidin-2-one (1.95 g, 11 mmol) and lithium chloride (0.47 g, 11 mmol) was added and the mixture was stirred for 18 hours. The precipitate was filtered and washed thoroughly with additional THF. The filtrate was concentrated in vacuo to give an oily solid. This solid was dissolved in 200 mL Et2O, washed successively with saturated NaHCO3, 0.5N HCl and saturated NaCl, dried (MgSO4) and concentrated in vacuo to give the title compound as an oil (3.0 g, 95%). 1HNMR (400 MHz; CDCl3): 0.73-0.84 (m, 12H), 1.10-1.22 (m, 4H), 1.46-1.54 (m, 2H), 2.75-2.87 (m, 2H), 4.70 (m, 1H, J=7 Hz), 5.59 (d, 1H, J=7 Hz), 7.22-7.37 (m, 5H). 5,5-Dimethyl-(S)-3-((R)-4-methyl-2-oxo-(S)-5-phenyl-oxazolidine-3-carbonyl)-octanoic acid tert-butyl ester: According to example 1, 5.07 g (16 mmol) of 3-(4,4-dimethyl-heptanoyl)-4-methyl-5-phenyl-oxazolidin-2-one, 18 mL (1N, 18 mmol) of NaHMDS solution and 4.72 mL (32 mmol) of bromo-acetic acid tert-butyl ester gave 3.40 g (49.3%) of the title compound as a crystalline solid. 1HNMR (400 MHz; CDCl3): 0.85-0.89 (m, 12H), 1.18-1.32 (m, 6H), 1.41 (s, 9H), 1.88 (dd, 1H, J=6 Hz, 8.4 Hz), 2.41 (dd, 1H, J=6 Hz, 16 Hz), 2.62 (dd, 1H, J=8.4 Hz, 16 Hz), 4.30-4.40 (m, 1H), 4.72 (m, 1H), 5.62 (d, 1H, J=7 Hz), 7.30-7.40 (m, 5H). m.p.: 83-85° C. (S)-2-(2,2-Dimethyl-pentyl)-succinic acid 4-tert-butyl ester: According to example 1, 3.4 g (7.9 mmol) of 5,5-dimethyl-3-(4-methyl-2-oxo-5-phenyl-oxazolidine-3-carbonyl)-octanoic acid tert-butyl ester, 16 mL (12.8 mmol) of 0.8N LiOH and 4.5 mL of 30% H2O2 gave 2.42 g (>100%) of the title compound as an oil. 1HNMR (400 MHz; CDCl3): 0.77-0.82 (m, 9H), 1.14-1.29 (m, 5H), 1.42 (s, 9H), 1.77 (dd, 1H, J=8 Hz, 16 Hz), 2.36 (dd, 1H, J=6 Hz, 16 Hz), 2.59 (dd, 1H, J=8 Hz, 16 Hz), 2.75-2.85 (m, 1H). (S)-3-Benzyloxycarbonylamino-5,5-dimethyl-octanoic acid tert-butyl ester: According to example 1, 2.149 (7.9 mmol) of 2-(2,2-dimethyl-pentyl)-succinic acid 4-tert-butyl ester, 1.7 mL of DPPA, 1.1 mL of Et3N and 2.44 mL of BnOH provided 1.639 (54.8% in two steps) of the title compound as an oil. 1HNMR (400 MHz; CDCl3): 0.78-0.89 (m, 9H), 1.10-1.30 (m, 5H), 1.36 (s, 9H), 2.39 (t, 2H, J=5 Hz), 4.95-4.05 (m, 1H), 5.00 (s, 2H), 5.09 (d, 1H, J=9.6 Hz), 7.22-7.30 (m, 5H). (S)-3-Amino-5,5-dimethyl-octanoic acid tert-butyl ester: According to example 1, 1.639 of 3-benzyloxycarbonylamino-5,5-dimethyl-octanoic acid tert-butyl ester and 0.29 of 20% Pd/C furnished the title compound. 1HNMR (400 MHz; CDCl3): 0.84-0.89 (m, 9H), 1.13-1.39 (m, 6H), 1.43 (s, 9H), 2.25 (dd, 1H, J=8.4 Hz, 15.6 Hz), 2.35 (dd, 1H, J=4.4 Hz, 15.6 Hz), 2.79 (s, br, 2H), 3.25-3.35 (m, 1H). MS, m/z, 244.2 (M+1)+. (S)-3-Amino-5,5-dimethyl-octanoic acid hydrochloride: According to example 1,3-amino-5,5-dimethyl-octanoic acid tert-butyl ester was treated with 3N HCl to provide 286 mg of the title compound as a solid. 1HNMR (400 MHz; CD3OD): 0.87-0.93 (m, 9H), 1.18-1.31 (m, 4H), 1.51 (dd, 1H, J=4 Hz, 14.4 Hz), 1.62 (dd, 1H, J=6.8 Hz, 14.4 Hz), 2.60 (dd, 1H, J=8 Hz, 17.6 Hz), 2.73 (dd, 1H, J=4 Hz, 7.6 Hz), 3.55-3.60 (m, 1H). MS (APCl), m/z 188.1 (M+1)+. 186.1 (M−1)+. Anal. Calc'd for C10H21NO2.HCl.0.12H2O: C, 53.17; H, 9.92, N, 6.20, Cl: 15.69; Found: C, 53.19; H, 10.00, N, 6.08, Cl: 15.25. α=+200 (MeOH). MP: 194.2-195.2° C.
