반응 #156711

반응 방정식

mixture

(2S,4R)-1-[3-(5-Bromo-3-fluoro-pyridin-2-yl)-azetidine-3-carbonyl]-4-(2-chloro-benzenesulfonyl)-pyrrolidine-2-carboxylic acid (1-cyano-cyclopropyl)-amide

sodium acetate

acetic acid

formaldehyde

sodium triacetoxyborohydride

→

title compound

수율 40.3%

(2S,4R)-1-[3-(5-Bromo-3-fluoro-pyridin-2-yl)-1-methyl-azetidine-3-carbonyl]-4-(2-chloro-benzenesulfonyl)-pyrrolidine-2-carboxylic acid (1-cyano-cyclopropyl)-amide

수율 40.3%

용매

dichloromethane

반응 조건

후처리

1. 1
   기타The cooling bath was removed after 10 min
2. 2
   workup.STIRRINGstirring
3. 3
   workup.WAITwas continued at 25° C. for further 18 h
4. 4
   기타The reaction mixture was quenched with aqueous 0.5 M NaOH-solution (2 ml)
5. 5
   workup.STIRRINGstirred for 2 min
6. 6
   기타the layers were separated
7. 7
   추출The aqueous layer was extracted with three portions of AcOEt (each 5 ml)
8. 8
   세척The combined organic layers were washed with brine
9. 9
   건조dried over Na2SO4
10. 10
    농축concentrated in vacuo
11. 11
    기타The crude material was purified by preparative HPLC

실험 절차

To a mixture of example 13 (0.05 g, 81.8 μmol, Eq: 1.00), sodium acetate (14.8 mg, 180 μmol, Eq: 2.2) and acetic acid (10.8 mg, 10.3 μl, 180 μmol, Eq: 2.2) in dichloromethane (0.5 ml) was added at 25° C. aqueous formaldehyde solution (36%; 19.1 mg, 17.5 μl, 229 μmol, Eq: 2.8). The mixture was stirred for 45 min, then sodium triacetoxyborohydride (55.5 mg, 262 μmol, Eq: 3.2) was added in one portion at 0-5° C. The cooling bath was removed after 10 min and stirring was continued at 25° C. for further 18 h. The reaction mixture was quenched with aqueous 0.5 M NaOH-solution (2 ml), stirred for 2 min, then the layers were separated. The aqueous layer was extracted with three portions of AcOEt (each 5 ml). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude material was purified by preparative HPLC to yield the title compound as a colorless amorphous solid (0.0206 g; 40%). m/z=626.1 [M+H]+.

출처