Reaktion #639411

Reaktionsgleichung

water

DCM

(S)-4-((S)-2-Amino-propyl)-6,6-dimethyl-morpholine-3 carboxylic acid (6-chloro-9H-beta-carbolin-8-yl)-amide hydrochloride salt

methyl chloroformate

→

desired product

Ausbeute 77.0%

{(S)-2-[(S)-5-(6-Chloro-9H-beta-carbolin-8-ylcarbamoyl)-2,2-dimethyl-morpholin-4-yl]-1-methyl-ethyl]-carbamic acid methyl ester

Ausbeute 77.0%

Lösungsmittel

pyridine

Reaktionsbedingungen

Aufarbeitung

1. 1
   Einengenthe mixture was concentrated to dryness
2. 2
   SonstigeThe residue was partitioned into 150 ml Of EtOAc and 100 ml of an aqueous 0.5M solution of K2CO3
3. 3
   ExtraktionThe separated aqueous phase was extracted with 50 ml of EtOAc
4. 4
   WaschenThe combined organic extracts were successively washed with water (2×50 ml) and brine (50 ml)
5. 5
   Trocknendried over Na2SO4
6. 6
   Einengenconcentrated to dryness
7. 7
   SonstigeThe residue was purified on silica (5% MeOH/CH2Cl2)

Vorschrift

To a solution of (S)-4-((S)-2-Amino-propyl)-6,6-dimethyl-morpholine-3 carboxylic acid (6-chloro-9H-beta-carbolin-8-yl)-amide hydrochloride salt (3.45 g, 6.59 mmole) in 68 ml of dry pyridine, was added in three portions over 1.5 hr, a 3M DCM solution of methyl chloroformate (9.2 ml, 27.6 mmole, 4.2 eq). After 2 h, 10 ml of water were added and the mixture was concentrated to dryness. The residue was partitioned into 150 ml Of EtOAc and 100 ml of an aqueous 0.5M solution of K2CO3. The separated aqueous phase was extracted with 50 ml of EtOAc. The combined organic extracts were successively washed with water (2×50 ml) and brine (50 ml), dried over Na2SO4 and concentrated to dryness. The residue was purified on silica (5% MeOH/CH2Cl2) to give 2.48 g (thick oil, 77% yield) of the desired product 1H-NMR (300 MHz, CDCl3): δ 1.15 (d, 3H), 1.28 (s, 3H), 1.42 (s, 3H), 2.33 (dd, 1H), 2.42 (d, 1H), 2.78 (dd, 1H), 2.86 (d, 1H), 3.32 (dd, 1H), 3.86 (s, 3H), 3.92 (t, 1H), 4.01 (dd, 1H), 4.18 (m, 1H), 4.78 (d, 1H), 7.95 (d, 1H), 7.97 (s, 1H), 8.29 (s, 1H), 8.50 (d, 1H), 8.98 (s, 1H), 9.88 (s, 1H), 10.94 (s, 1H). Retention Time (LC, method: ammonium acetate standard): 1.70 min. MS (M+H+): 474.1

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