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 80975Notes

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]oxazin-an-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-e1240800a6dd439090f990c3e42af3e9
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846668B2

Reaction notes

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