tert-butyl N-(6-hydroxyhexyl)carbamate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: methyl 4-(4-chloro-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)-2-hydroxybenzoate (100 mg, 0.264 mmol), tert-butyl 6-hydroxyhexylcarbamate (68.9 mg, 0.317 mmol), Triphenylphosphine (139 mg, 0.528 mmol), were dissolved in DCM then DIAD (0.103 mL, 0.528 mmol) was added. The reaction was stirred for 16 h. The solvent was removed under vacuum and the crude product was purified by silica gel chromatography using 20% EtOAc/Hexanes. The product fractions were collected and the solvent was removed under vacuum to give 55 mg (36%) methyl 2-(6-(tert-butoxycarbonylamino)hexyloxy)-4-(4-chloro-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)benzoate. The solvent was removed under vacuum the crude product was purified by silica gel chromatography The product fractions were collected the solvent was removed under vacuum

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of tert-butyl 6-hydroxyhexylcarbamate (21 mmol) in CH2Cl2 (30 ml) was added imidazole (27 mmol) at 0° C. The reaction mixture was kept at 25° C. and stirred for 20 min, then cooled to 0° C. To the resulting reaction mixture was added tert-butyldimethylchlorosilane (23 mmol) dropwise over 30 min at 0° C. The reaction mixture was allowed to warm to 25° C. and stirred for 16 h and then filtered. The filtrate was washed with 1 N HCl (2×25 ml) and brine (30 ml), dried over Na2SO4, filtered and evaporated under reduced pressure. The residue was purified by SiO2 flash column (eluent: petroleum ether and then CH2Cl2). Yield 6.53 g (87% yield). was kept at 25° C. To the resulting reaction mixture to warm to 25° C. stirred for 16 h filtered The filtrate was washed with 1 N HCl (2×25 ml) and brine (30 ml) dried over Na2SO4 filtered evaporated under reduced pressure The residue was purified by SiO2 flash column (eluent

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1.0 g of 6-tert-butoxycarbonylamino-1-hexanol in 20 mL of methylene chloride was combined with 3 g of a 4 angstrom molecular sieve, 808 mg of N-methylmorpholine-N-oxide and a catalytic amount of tetrapropylammonium perruthenate, and stirred for 24 hours. The reaction solution was filtered through Celite, and concentrated. The residue was purified by column chromatography on silica gel (n-hexane:ethyl acetate=2:1) to obtain 660 mg of the desirable compound. The reaction solution was filtered through Celite concentrated The residue was purified by column chromatography on silica gel (n-hexane:ethyl acetate=2:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of tert-butyl (6-hydroxyhexyl)carbamate (12.18 g, 56.05 mmol) and TEA (8.51 g, 84.08 mmol) in 100 ml of methylene chloride, methanesulfonyl chloride (9.63 g, 84.08 mmol) was slowly added at 0° C. The mixture was stirred at room temperature overnight. The compound was purified by silica chromatography using heptane/ethyl acetate as eluent. The compound was purified by silica chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of tert-butyl (6-hydroxyhexyl)carbamate (12.18 g, 56.05 mmol) and TEA (8.51 g, 84.08 mmol) in 100 ml of methylene chloride, methanesulfonyl chloride (9.63 g, 84.08 mmol) was slowly added at 0° C. The mixture was stirred at room temperature overnight. The compound was purified by silica chromatography using heptane/ethyl acetate as eluent. The compound was purified by silica chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of compound 2 (1 g, 4.61 mmol) in toluene (30 mL) were added Ph3P (1.81 g, 6.91 mmol) and CBr4 (2.29 g, 6.91 mmol) at RT under inert atmosphere and stirred for 3 h. The mixture was diluted with water (50 mL) and extracted with EtOAc (3×60 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo to obtain the crude. The crude was purified (silica gel; 20% EtOAc/hexanes) to afford compound 3 (1 g, 78%) as colorless oil. 1H NMR (400 MHz, CDCl3): δ 4.51 (br s, 1H), 3.40 (t, J=6.8 Hz, 2H), 3.13-3.08 (m, 2H), 1.89-1.82 (m, 2H), 1.52-1.42 (m, 13H), 1.37-1.31 (m, 2H). extracted with EtOAc (3×60 mL) The combined organic extracts were dried over Na2SO4 filtered concentrated in vacuo to obtain the crude The crude was purified (silica gel; 20% EtOAc/hexanes)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: methyl 4-(4-chloro-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)-2-hydroxybenzoate (100 mg, 0.264 mmol), tert-butyl 6-hydroxyhexylcarbamate (68.9 mg, 0.317 mmol), Triphenylphosphine (139 mg, 0.528 mmol), were dissolved in DCM then DIAD (0.103 mL, 0.528 mmol) was added. The reaction was stirred for 16 h. The solvent was removed under vacuum and the crude product was purified by silica gel chromatography using 20% EtOAc/Hexanes. The product fractions were collected and the solvent was removed under vacuum to give 55 mg (36%) methyl 2-(6-(tert-butoxycarbonylamino)hexyloxy)-4-(4-chloro-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)benzoate. The solvent was removed under vacuum the crude product was purified by silica gel chromatography The product fractions were collected the solvent was removed under vacuum

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir: