Reaktion #69355

Reaktionsgleichung

4-chlorobenzylamine

iPr2NEt

trifluoroacetic acid

2-((3R,11S,E)-5,12-dioxo-3-phenyl-1-oxa-4-azacyclododec-8-en-11-yl)acetic acid

EDC

HOBt

tert-butyl 2-((3R,11S,E)-5,12-dioxo-3-phenyl-1-oxa-4-azacyclododec-8-en-11-yl)acetate

→

desired product

N-(4-chlorobenzyl)-2-((3R,11S,E)-5,12-dioxo-3-phenyl-1-oxa-4-azacyclododec-8-en-11-yl)acetamide

Lösungsmittel

CH2Cl2

CH2Cl2

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeconsumption of starting material
2. 2
   EinengenThe reaction mixture was concentrated
3. 3
   workup.ADDITIONwere subsequently added
4. 4
   workup.STIRRINGstirred for 16 h at which point LC-MS analysis
5. 5
   Sonstigeconsumption of starting material
6. 6
   workup.ADDITIONThe reaction mixture was diluted with saturated NH4Cl and EtOAc
7. 7
   Sonstigethe layers separated
8. 8
   ExtraktionThe aqueous was extracted 2× with EtOAc
9. 9
   Waschenthe combined organic extracts were washed with 1 N HCl and brine
10. 10
    Trocknendried over Na2SO4
11. 11
    Filtrationfiltered
12. 12
    Einengenconcentrated
13. 13
    SonstigeThe crude product was purified

Vorschrift

To a solution of tert-butyl 2-((3R,11S,E)-5,12-dioxo-3-phenyl-1-oxa-4-azacyclododec-8-en-11-yl)acetate (130 mg, 0.336 mmol) in CH2Cl2 (258 μL) cooled in an ice/water bath was added trifluoroacetic acid (116 μL, 1.510 mmol) and the reaction mixture was stirred 1 h at which point LC-MS analysis indicated complete consumption of starting material. The reaction mixture was concentrated and the crude carboxylic acid was utilized immediately. To a solution of crude 2-((3R,11S,E)-5,12-dioxo-3-phenyl-1-oxa-4-azacyclododec-8-en-11-yl)acetic acid (111 mg, 0.335 mmol) in CH2Cl2 (4.2 mL) cooled in an ice/water bath was added EDC (64.2 mg, 0.335 mmol) and HOBt (45.3 mg, 0.335 mmol) and the resulting solution was stirred 30 min 4-chlorobenzylamine (41.0 μL, 0.335 mmol), iPr2NEt (176 μL, 1.005 mmol) and DMAP (4.09 mg, 0.033 mmol) were subsequently added and the reaction mixture was slowly warmed to rt and stirred for 16 h at which point LC-MS analysis indicated complete consumption of starting material. The reaction mixture was diluted with saturated NH4Cl and EtOAc and the layers separated. The aqueous was extracted 2× with EtOAc and the combined organic extracts were washed with 1 N HCl and brine, dried over Na2SO4, filtered, and concentrated. The crude product was purified using silica gel chromatography (MeOH/CH2Cl2 gradient) to yield the desired product as a white solid. 1H NMR (300 MHz, (CD3)2SO): δ 1.95-2.57 (m, 7H), 2.73-2.80 (m, 1H), 3.65 (dd, 1H, J=3.6, 11.3), 4.20 (s, 1H), 4.22 (s, 1H), 4.61 (apparent triplet, 1H, J=11.3), 5.23-5.34 (m, 3H), 7.22-7.24 (m, 9H), 8.25 (d, 1H, J=9.5), 8.41-8.46 (m, 1H); LRMS (M+H)+: 455.1.

Quelle