tert-butyl N-[(2S)-1-hydroxyhexan-2-yl]carbamate

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To as stirred solution of Boc-L-Nle-ol (0.50 g, 1.9 mmol) in dry tetrahydrofuran (15 mL), cooled at 0° C. under nitrogen, NaH (0.05 g, 2.1 mmol) was added. The reaction mixture was stirred for 45 min at 0° C., followed by addition of 18-crown-6 (0.25 g, 0.9 mmol) and subsequently a solution of ethyl bromoacetate (0.47 g, 2.8 mmol) in dry tetrahydrofuran (4 mL) was added dropwise at 0° C. The reaction mixture was stirred for 1 h at 0° C. and overnight at room temperature. The organic solvent was evaporated under reduced pressure and the residue was purified by column-chromatography using chloroform as eluent. Yield 55%; Oil; [a]D=−13.9 (c 1CHCl3); 1H NMR (200 MHz, CDCl3) δ 4.85-4.78 (m, 1H), 4.17 (q, J=7.4 Hz, 2H), 4.03 (s, 2H), 3.72-3.58 (m, 1H), 3.56-3.41 (m, 2H), 1.62-1.21 (m, 18H), 0.85 (t, J=6.6 Hz, 3H); 13C NMR (50 MHz, CDCl3) δ 170.3, 155.6, 78.9, 73.3, 68.4, 60.7, 50.3, 31.5, 28.3, 28.1, 22.5, 14.1, 13.9. Anal. Calcd for C15H29NO5: C, 59.38; H, 9.63; N, 4.62. Found: C, 59.16; H, 9.82; N, 4.51. The reaction mixture was stirred for 1 h at 0° C. and overnight at room temperature The organic solvent was evaporated under reduced pressure the residue was purified by column-chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The same reaction procedure as in Reference Example 12 was repeated except that (S)-2-[N-(2-methyl-2-propyloxycarbonyl)amino]hexanol used in Reference Example 12 was replaced by 14.33 g of (S)-2-[N-(2-methyl-2-propyloxycarbonyl) amino]propanol, whereby 6.95 g of the captioned (2RS,3S)-N-cyclopentyl-3-amino-2-hydroxybutanamide was obtained in a yield of 45%. 1H-NMR (CDCl3, δ): 1.05 (3/2H, d, J=7 Hz), 1.15 (3/2H, d, J=7 Hz), 1.35-1.50 (2H, m), 1.55-1.76 (4H, m), 1.90-2.10 (2H, m), 3.31-3.41 (1/2H, m), 3.48-3.52 (1/2H, m), 3.74 (1/2H, d, J=3 Hz), 3.87 (1/2H, d, J=5 Hz), 4.13-4.29 (1H, m), 7.18 (1/2H, d, J=8 Hz), 7.25 (1/2H, d, J=8 Hz). The same reaction procedure as in Reference Example 12

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The same reaction procedure as in Reference Example 12 was repeated except that (S)-2-[N-(2-methyl-2-propyloxycarbonyl)amino]hexanol used in Reference Example 12 was replaced by 7.53 g of (S)-2-[N-(2-methyl-2-propyloxycarbonyl) amino]-4-(methylthio)butanol, whereby 3.22 g of the captioned (2RS,3S)-N-cyclopentyl-3-amino-2-hydroxy-5-(methylthio)pentanamide was obtained in a yield of 42%. The same reaction procedure as in Reference Example 12

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 40 g (200 mmol) of (S)-2-[N-(2-methyl-2-propyloxycarbonyl)amino]hexanol was dissolved in 300 ml of anhydrous methylenechroride, 34 g (400 mmol) of acetone cyanhydrin and 12.1 g (120 mmol) of triethylamine were added to the above-prepared reaction solution, followed by stirring for one night. The reaction solution was concentrated under reduced pressure. The residue thus obtained was washed with 300 ml of ether in addition to distilled water and dried over anhydride sodium sulfate and concentrated under reduced pressure. The residue was separated out by silica gel column chromatography, whereby 38.7 g of (2RS,3S)-2-hydroxy-3-[N-(2-methyl-2-propyloxycarbonyl)amino]heptanenitrile was obtained. were added to the above-prepared reaction solution The reaction solution was concentrated under reduced pressure The residue thus obtained was washed with 300 ml of ether in addition to distilled water dried over anhydride sodium sulfate concentrated under reduced pressure The residue was separated out by silica gel column chromatography