Reaktion #161921

Reaktionsgleichung

#11

(2R,3R)-3-[(2S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl]-3-methoxy-2-methylpropanoic acid

diisopropylethylamine

L-phenylalanine methyl ester hydrochloride

HATU

→

#37

Ausbeute 65.5%

methyl N-{(2R,3R)-3-[(2S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl]-3-methoxy-2-methylpropanoyl}-L-phenylalaninate

Ausbeute 65.5%

Lösungsmittel

dichloromethane

N,N-dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   Einengenconcentrated in vacuo
2. 2
   Waschenwashed sequentially with 1 M hydrochloric acid (2×50 mL) and brine
3. 3
   TrocknenThe organic layer was dried over sodium sulfate
4. 4
   Filtrationfiltered
5. 5
   Sonstigeevaporated in vacuo
6. 6
   Filtrationfiltered
7. 7
   SonstigeThe filtrate was purified by silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane)

Vorschrift

To a mixture of #11 (2.7 g, 9.4 mmol, 1 eq.) in dichloromethane (30 mL, 0.3 M) and N,N-dimethylformamide (3 mL) were added diisopropylethylamine (3.30 mL, 18.8 mmol, 2 eq.), L-phenylalanine methyl ester hydrochloride (2.03 g, 9.40 mmol, 1.2 eq.) and HATU (4.79 g, 12.2 mmol, 1.3 eq.). The reaction was stirred for 18 hours and then concentrated in vacuo. The residue was taken up in ethyl acetate (100 mL) and washed sequentially with 1 M hydrochloric acid (2×50 mL) and brine. The organic layer was dried over sodium sulfate, filtered and evaporated in vacuo. The crude material was taken up in dichloromethane and filtered. The filtrate was purified by silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane) to give #37 (2.76 g, 65%) as an off-white solid. LC-MS: m/z 449.3 [M+H+], 349.2 [(M−Boc)+H+] retention time=0.88 minutes; 1H NMR (400 MHz, DMSO-d6), presumed to be a mixture of rotamers, characteristic signals: δ 8.28 (d, J=8.2 Hz, 1H), 7.14-7.29 (m, 5H), 4.50 (ddd, J=10.9, 8.1, 4.4 Hz, 1H), 3.64 (s, 3H), 3.23 (s, 3H), 2.15-2.24 (m, 1H), 1.56-1.76 (m, 2H), 1.31-1.55 (m, 11H), 1.02 (d, J=6.6 Hz, 3H).

Quelle