Trimethyl orthoacetate → (S)-6-(2-Methyl-allyl)-3-{(S)-1-[4-(5-methyl-[1,3,4]oxadiazol-2-yl)-phenyl]-ethyl}-6-phenyl-[1,3]oxazinan-2-one

HRID 2037830Notes

Reaction equation

O[C:2]([CH3:30])([CH3:29])[CH2:3][C@@:4]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:22]=[CH:21][C:16]([C:17]([NH:19][NH2:20])=[O:18])=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1.O.[C:32]1(C)C=CC(S(O)(=O)=O)=C[CH:33]=1.COC(OC)(OC)C>C(OCC)(=O)C>[CH3:29][C:2](=[CH2:30])[CH2:3][C@:4]1([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:22]=[CH:21][C:16]([C:17]3[O:18][C:32]([CH3:33])=[N:20][N:19]=3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 4-{(S)-1-[(S)-6-(2-hydroxy-2-methyl-propyl)-2-oxo-6-phenyl-[1,3]oxazinan-3-yl]-ethyl}-benzoic acid hydrazide (90 mg), toluene-4-sulfonic acid monohydrate (10 mg), and 1,1,1-trimethoxy-ethane (1 ml) was stirred at room temperature for 1 h, at 80° C. for 2 h, and finally at reflux temperature for 1.5 h. After cooling to ambient temperature, ethyl acetate was added and the resulting mixture was washed with aqueous NaHCO3 solution and brine. The solvent was removed under reduced pressure and the residue was purified by chromatography on silica gel (CH2Cl2/MeOH 99:1→95:5) to afford the title compound as a colorless resin-like solid.

Workup

temperaturefinally at reflux temperature for 1.5 h
temperatureAfter cooling to ambient temperature
washthe resulting mixture was washed with aqueous NaHCO3 solution and brine
customThe solvent was removed under reduced pressure
customthe residue was purified by chromatography on silica gel (CH2Cl2/MeOH 99:1→95:5)

Sources & evidence

ORD record: ord-4ccf6ced88f845bc911d6fba38a29f93
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08575156B2

Reaction notes

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