Реакция #1366985

Уравнение реакции

O-(Trimethylsilyl)hydroxylamine

(3R)-6-cyclobutyl-3-{4-[(dimethylamino)carbonyl]-1,3-oxazol-2-yl}hexanoic acid

N-methylmorpholine

isobutyl chloroformate

→

title compound

Выход 39.6%

2-{(1R)-4-Cyclobutyl-1-[2-(hydroxyamino)-2-oxoethyl]butyl}-N,N-dimethyl-1,3-oxazole-4-carboxamide

Выход 39.6%

Растворители

tetrahydrofuran

methanol

Условия реакции

Обработка

1. 1
   workup.STIRRINGthe mixture was stirred for 18 hours
2. 2
   workup.STIRRINGstirred at room temperature for 10 minutes
3. 3
   ДругоеThe solvent was removed under reduced pressure
4. 4
   workup.DISSOLUTIONThe residue was dissolved in ethyl acetate
5. 5
   Промывкаwashed with water
6. 6
   Сушкаdried over anhydrous sodium sulphate
7. 7
   Фильтрацияfiltered
8. 8
   Другоеthe solvent removed under reduced pressure
9. 9
   ДругоеThe oil was purified by column chromatography on silica gel eluting with a gradient system of 98:2 (dichloromethane:methanol)
10. 10
    ДругоеThe solid was triturated with diethyl ether
11. 11
    Фильтрацияfiltered
12. 12
    Другоеdried under reduced pressure

Методика

A solution of (3R)-6-cyclobutyl-3-{4-[(dimethylamino)carbonyl]-1,3-oxazol-2-yl}hexanoic acid (Preparation 121) (155 mg, 0.50 mmol) and N-methylmorpholine (90 μl, 0.82 mmol) in anhydrous tetrahydrofuran (8 ml) was cooled to 0° C., treated with isobutyl chloroformate (90 μl, 0.70 mmol) and stirred under a nitrogen atmosphere for 2 hours. O-(Trimethylsilyl)hydroxylamine (200 μl, 1.63 mmol) was added and the mixture was stirred for 18 hours, being allowed to warm to room temperature over this time. The mixture was then treated with methanol (2 ml) and stirred at room temperature for 10 minutes. The solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate and washed with water, dried over anhydrous sodium sulphate, filtered and the solvent removed under reduced pressure. The oil was purified by column chromatography on silica gel eluting with a gradient system of 98:2 (dichloromethane:methanol) gradually changing to 90:10 (dichloromethane:methanol). The solid was triturated with diethyl ether, filtered and dried under reduced pressure to afford the title compound as a white solid (64 mg).

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