Reaktion #161900

Reaktionsgleichung

#4

tert-butyl (3R,4S,5S)-3-methoxy-5-methyl-4-(methylamino)heptanoate, hydrochloride salt

N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-valine

2-chloro-4,6-dimethoxy-1,3,5-triazine

N-methylmorpholine

→

#5

Ausbeute 113.1%

tert-butyl (3R,4S,5S)-4-[{N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-valyl}(methyl)amino]-3-methoxy-5-methylheptanoate

Ausbeute 113.1%

Lösungsmittel

2-methyltetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe reaction was quenched with water (50 mL)
2. 2
   SonstigeThe aqueous layer was separated
3. 3
   Extraktionback-extracted with 2-methyltetrahydrofuran (50 mL)
4. 4
   WaschenThe combined organic layers were washed with saturated aqueous sodium bicarbonate solution (50 mL)
5. 5
   Trocknendried over magnesium sulfate
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated in vacuo
8. 8
   Sonstigeto give a colorless oil, which
9. 9
   Sonstigewas purified by silica gel chromatography (Gradient: 5% to 40% ethyl acetate in heptane)

Vorschrift

To a mixture of N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-valine (18.53 g, 54.60 mmol, 1.3 eq.) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) (9.58 g, 54.6 mmol, 1.3 eq.) in 2-methyltetrahydrofuran (118.00 mL, 0.34 M) was added N-methylmorpholine (6.52 mL, 59.1 mmol, 1.5 eq.) followed by #4 (11.80 g, 39.9 mmol, 1 eq.). After 3 hours, the reaction was quenched with water (50 mL) and stirred for 15 minutes. The aqueous layer was separated and back-extracted with 2-methyltetrahydrofuran (50 mL). The combined organic layers were washed with saturated aqueous sodium bicarbonate solution (50 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo to give a colorless oil, which was purified by silica gel chromatography (Gradient: 5% to 40% ethyl acetate in heptane) to give #5 (26.2 g, 91%) as a colorless foam. LC-MS (Protocol I) m/z 581.3 [M+H+] 1604.3 [M+Na+], retention time=4.993 minutes; 1H NMR (400 MHz, DMSO-d6), possibly a mixture of rotamers, characteristic major signals: δ 7.88 (d, J=7.4 Hz, 2H), 7.71 (d, J=7.4 Hz, 2H), 7.62 (d, J=8.6 Hz, 1H), 7.41 (dd, J=7.4, 7.4 Hz, 2H), 7.27-7.34 (m, 2H), 4.13-4.32 (m, 4H), 3.70-3.82 (br m, 1H), 3.24 (s, 3H), 2.92 (br s, 3H), 2.54 (dd, J=15.7, 2.4 Hz, 1H), 2.17 (dd, J=15.4, 9.4 Hz, 1H), 1.95-2.07 (m, 1H), 1.70-1.83 (br m, 1H), 1.40 (s, 9H), 0.83-0.94 (m, 9H), 0.69 (t, J=7.2 Hz, 3H).

Quelle