(2S,4S)-(+)-戊二醇

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 10 g of (+)-(2S,4S)pentane-2,4-diol and 13.6 g of trimethylphosphite were mixed, and heated at 100° C. on an oil bath. After completion of distilling methanol off, the residue is distilled under reduced pressure to obtain colorless transparent 2-methoxy-(4S,6S)-4,6-dimethyl-1,3,2-dioxaphosphorinane. bp: 70°-72° C./15 mmHg. After completion of distilling methanol off, the residue is distilled under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 15.6 g (0.105 mol) of 1,1,1-trimethoxyisobutane, 10 g (0.0962 mol) of 2(S),4(S)-dihydroxypentane, and 251 mg of PPTS in 150 ml of toluene (dried over 3° A sieves) was allowed to reflux under argon for 11/2 hours while azeotroping water formed using the Dean-Stark trap. The reaction mixture was cooled, 1.2 g of potassium tert. butoxide was added, and the solvent was distilled. Ether (100 ml) was added to the residue, passed through a supercel pad eluting with 300 ml of ether, and the combined solvent was distilled in vacuo (<40° C.). The residue was distilled to afford 14.3 g (79.4%) of 2-isopropyl-2-methoxy-4(R),6(R)-dimethyl-1,3-dioxane, b.p. 78°-82° C./15 mm. dried over 3° A sieves) to reflux under argon for 11/2 hours while azeotroping water formed The reaction mixture was cooled the solvent was distilled Ether (100 ml) was added to the residue eluting with 300 ml of ether the combined solvent was distilled in vacuo (<40° C.) The residue was distilled

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 1-benzyl-3-methylpiperidin-4-one (Acros, 62.09 g, 305.4 mmol) and (2S,4S)-pentane-2,4-diol (TCI-US, 34.06 g, 327.0 mmol) in benzene (800 mL) was added p-toluenesulfonic acid mono hydrate (69.72 g, 404.9 mmol). The flask was fitted with a Dean-Stark trap and heated to reflux. The reaction mixture was cooled after 16 hours of reflux, concentrated to a total volume of about 500 mL and transferred to an Erlenmeyer flask with ethyl acetate. A sodium bicarbonate solution (500 mL) added with stirring and the mixture was further neutralized with solid Na2CO3 (35 g). The layers were partitioned, the organic phase washed with sodium bicarbonate, dried (Na2SO4) and concentrated to yield approximately 95 g of crude material. The residue was purified in 15 g batches by silica gel chromatography (Analogix SF-65-600 g; 35 micron silica; elution with 10% ethyl acetate-hexane) at 50 mL/min to provide 42.33 g of the first eluting isomer, (2S,4S,7R)-9-benzyl-2,4,7-trimethyl-1,5-dioxa-9-azaspiro[5.5]undecane. 1H NMR (300 MHz, DMSO-d6) δ 7.33-7.19 (m, 5H), 4.07-3.86 (m, 2H), 3.40 (ABq, 2H, JAB=13.5 Hz, δνAB=23.3 Hz), 2.41-2.20 (m, 4H), 1.90-1.76 (m, 2H), 1.59-1.47 (m, 3H), 1.12 (d, 3H, J=6.4 Hz), 1.11 (d, 3H, J=6.4 Hz), 0.90 (d, 3H, J=7.1 Hz); MS (DCI/NH3) m/e 290 (M+H)+. The flask was fitted with a Dean-Stark trap heated to reflux The reaction mixture was cooled after 16 hours of reflux concentrated to a total volume of about 500 mL A sodium bicarbonate solution (500 mL) added The layers were partitioned the organic phase washed with sodium bicarbonate dried (Na2SO4) concentrated to yield approximately 95 g of crude material The residue was purified in 15 g batches by silica gel chromatography (Analogix SF-65-600 g; 35 micron silica; elution with 10% ethyl acetate-hexane) at 50 mL/min