4-Methylmorpholine → HCID 9923241, compound

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).

1. stirringthe mixture was stirred for 18 hours
2. stirringstirred at room temperature for 10 minutes
3. customThe solvent was removed under reduced pressure
4. dissolutionThe residue was dissolved in ethyl acetate
5. washwashed with water
6. dry with materialdried over anhydrous sodium sulphate
7. filtrationfiltered
8. customthe solvent removed under reduced pressure
9. customThe oil was purified by column chromatography on silica gel eluting with a gradient system of 98:2 (dichloromethane:methanol)
10. customThe solid was triturated with diethyl ether
11. filtrationfiltered
12. customdried under reduced pressure

ORD record

ord-a4d919952d3c4e0a879fbb1beb7cc974

Source dataset

uspto-grants-2002_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06448278B2