Hexamethylenetetramine → ethyl 2-[(1R)-1-(2-tert-butoxy-2-oxoethyl)-4-cyclohexylbutyl]-1,3-oxazole-4-carboxylate

A suspension of CuBr2 (20.88 g, 93.5 mmol) and HMTA (13.1 g, 93.5 mmol) in degassed DCM (250 ml) was treated with DBU (14.0 ml, 93.5 mmol) and the dark solution formed was stirred in a water bath for 5 minutes. A solution of ethyl(4S)-2-[(1R)-1-(2-tert-butoxy-2-oxoethyl)-4-cyclohexylbutyl]-4,5-dihydro-1,3-oxazole-4-carboxylate (preparation 152) (9.24 g, 23.4 mmol) in degassed DCM (30 ml) was added dropwise to the reaction mixture and stirred at room temperature for a further 3 hours. The solvent was removed under reduced pressure. The residue was dissolved in EtOAc and washed with a 1:1 solution of NH3(aq): NH4Cl. The aqueous extract was washed with EtOAc (2×380 ml). The combined organic extracts were washed with 2M HCl (500 ml), sat. NaHCO3 (500 ml) and brine (500 ml). The organic extracts were dried over anhydrous MgSO4 and filtered. The solvent was removed under reduced pressure. The crude material was purified on a silica column eluting with a solvent gradient of EtOAc:pentane (0:100) gradually changing to (25:75) to afford the title compound as colourless oil which formed needles on standing (7.39 g, 80%).

1. customthe dark solution formed
2. stirringstirred at room temperature for a further 3 hours
3. customThe solvent was removed under reduced pressure
4. dissolutionThe residue was dissolved in EtOAc
5. washwashed with a 1:1 solution of NH3(aq)
6. extractionThe aqueous extract
7. washwas washed with EtOAc (2×380 ml)
8. washThe combined organic extracts were washed with 2M HCl (500 ml), sat. NaHCO3 (500 ml) and brine (500 ml)
9. dry with materialThe organic extracts were dried over anhydrous MgSO4
10. filtrationfiltered
11. customThe solvent was removed under reduced pressure
12. customThe crude material was purified on a silica column
13. washeluting with a solvent gradient of EtOAc:pentane (0:100)

ORD record

ord-36debad6573b4ca7a944347756bff669

Source dataset

uspto-grants-2007_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07214694B2