Reaktion #975408

Reaktionsgleichung

(5S)-2,2-dimethyl-5-((1R)-3-methyl-1-{[(2R)-2-methyl-4-(2-pyridinyl)piperazinyl]carbonyl}butyl)-1,3-dioxolan-4-one

hydroxylamine

→

title product ( 4 )

Ausbeute 47.5%

(2S,3S)-N,2-dihydroxy-5-methyl-3-{[(2R)-2-methyl-4-(2-pyridinyl)piperazinyl]carbonyl}hexanamide

Ausbeute 47.5%

Lösungsmittel

water

iPrOH

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe resulting reaction mixture
2. 2
   Sonstigedirectly purified by reverse-phase chromatography (major diastereoisomer as the first eluted peak
3. 3
   workup.WAITgradient starting from 100% H2O up to 75% H2O in ACN in 5 min
4. 4
   workup.WAITisocratic 75% H2O in ACN for 25 min

Vorschrift

To a solution of (5S)-2,2-dimethyl-5-((1R)-3-methyl-1-{[(2R)-2-methyl-4-(2-pyridinyl)piperazinyl]carbonyl}butyl)-1,3-dioxolan-4-one (517 mg; 1.33 mmol; 1.0 eq) in iPrOH (2.0 mL) was added an aqueous solution of hydroxylamine (391.5 μl; 6.64 mmol; 5.0 eq.) and the resulting reaction mixture was stirred at RT for 40 min. HPLC analyses showed the presence of 2 diastereoisomers (75/25). This reaction mixture was dissolved in water (6 mL) and directly purified by reverse-phase chromatography (major diastereoisomer as the first eluted peak, gradient starting from 100% H2O up to 75% H2O in ACN in 5 min, then isocratic 75% H2O in ACN for 25 min; flow: 50 mL/min) to give the title product (4) as a white powder (230 mg; 47%). 1H NMR (CD3OD, 300 MHz) δ 8.10 (m, 1H), 7.58 (m, 1H), 6.84 (m, 1H), 6.69 (m, 1H), 4.84-4.70 (m, 1H), 4.60 (m, 1H), 4.48 (m, 0.4H), 4.19 (m, 1H), 4.13-3.98 (m, 2H), 3.71-3.55 (m, 0.6H), 3.30-3.07 (m, 2H), 3.05-2.82 (m, 1H), 1.94-1.76 (m, 1H), 1.55-1.38 (m, 3H), 1.35 (d, 1.3H, J=6.7 Hz), 1.23 (d, 1.7H, J=6.7 Hz), 0.93 (m, 6H). M+(ESI): 365.2, M−(ESI): 363.2. HPLC (Condition B), Rt: 2.4 min (HPLC purity: 97.6%).

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