反应详情

To a solution of 0.5 g of L-phenylalanine t-butyl ester hydrochloride in 4 mL of N,N-dimethylformamide were added 0.67 g of 4-methoxy-2,3,6-trimethylphenylsulfonylchloride and 0.96 mL of N,N-diisopropylethylamine. After stirring for 2 hours at room temperature the reaction mixture was concentrated and the residue dissolved in ethyl acetate. The ethyl acetate solution was washed with aqueous potassium hydrogensulfate (5%), water, aqueous sodium hydrogencarbonate (5%) and brine, dried over magnesium sulfate and concentrated, The residue was dissolved in 16 mL of dichloromethane and 4 mL of trifluoroacetic acid was added. After stirring for 2h at room temperature the reaction mixture was concentrated. Dichloromethane and aqueous sodium hydrogencarbonate (5%) were added to the residue (the mixture was basic), the aqueous layer separated and washed with dichloromethane. The aqueous layer was made acid (pH 2) using 2 N hydrochloric acid and several times extracted with dichloromethane. The combined dichloromethane layers were washed with brine, dried over magnesium sulfate and concentrated to give 0.65 g of (2S)-2-[[(4-methoxy-2,3,6-trimethylphenyl)sulfonyl]amino]-3-phenylpropanoic acid. This acid (80 mg) was coupled with deprotected 5a (75 mg) according to the procedure described for 5c to afford compound 55 (55 mg) as a mixture of diastereomers (1:1). 1H-NMR 400 MHz (CD3OD) δ: 1.25-1.67 (6H, m), 1.97 and 1.99 (3H, 2x s), 2.12 and 2.17 (3H, 2x s), 2.45-3.54 (8H, m), 2.49 (3H, s), 3.81 and 3.85 (3H, 2x s), 3.82-3.92 (1H, m), 5.13-5.28 (1H, m), 6.61 (1H, s), 6.84-7.07 (5H, m), 7.17-7.21 (1H, m), 7.50-7.56 (1H, m), 7.65-7.69 (1H, m), 7.76-7.82 (1H, m), 8.30-8.35 (1H, m).

1. concentrationwas concentrated
2. dissolutionthe residue dissolved in ethyl acetate
3. washThe ethyl acetate solution was washed with aqueous potassium hydrogensulfate (5%), water, aqueous sodium hydrogencarbonate (5%) and brine
4. dry with materialdried over magnesium sulfate
5. concentrationconcentrated
6. dissolutionThe residue was dissolved in 16 mL of dichloromethane
7. addition4 mL of trifluoroacetic acid was added
8. stirringAfter stirring for 2h at room temperature the reaction mixture
9. concentrationwas concentrated
10. additionDichloromethane and aqueous sodium hydrogencarbonate (5%) were added to the residue (the mixture
11. customseparated
12. washwashed with dichloromethane
13. extractionextracted with dichloromethane
14. washThe combined dichloromethane layers were washed with brine
15. dry with materialdried over magnesium sulfate
16. concentrationconcentrated