Tetrahydro-2H-pyran-4-carboxaldehyde → 2-Methoxycarbonylamino-3-(tetrahydro-pyran-4-yl)-acrylic acid methyl ester

HRID 1751451Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:16])[CH:4](P(OC)(OC)=O)[NH:5][C:6]([O:8][CH3:9])=[O:7].CC(C)=O.C(=O)=O.[O:24]1[CH2:29][CH2:28][CH:27]([CH:30]=O)[CH2:26][CH2:25]1>C1COCC1.CCOC(C)=O>[CH3:1][O:2][C:3](=[O:16])[C:4]([NH:5][C:6]([O:8][CH3:9])=[O:7])=[CH:30][CH:27]1[CH2:28][CH2:29][O:24][CH2:25][CH2:26]1

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of (Dimethoxy-phosphoryl)-methoxycarbonylamino-acetic acid methyl ester (0.34 g, 1.35 mmol) in THF (5.4 mL) at −78° C. (external, Acetone/CO2 bath) was added 1,1,3,3-tetramethguanidine (0.17 mL, 1.35 mmol). The solution was stirred for 15 min before Tetrahydro-pyran-4-carbaldehyde (0.15 g, 1.35 mmol) was added. The reaction was stirred at −78° C. for 2 h and then allowed to warm to room temperature. The reaction was diluted with EtOAc and washed with HCl (1N) and brine. The aqueous layers were back extracted with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated. The crude oil was purified by column chromatography (SiO2, 20→100% EtOAc in Hexanes) to provide 2-Methoxycarbonylamino-3-(tetrahydro-pyran-4-yl)-acrylic acid methyl ester (0.15 g, 45%). LCMS-ESI+: calc'd for C11H17NO5: 243.11 (M+); Found: 243.96 (M+H+).

Workup

additionwas added
temperatureto warm to room temperature
washwashed with HCl (1N) and brine
extractionThe aqueous layers were back extracted with EtOAc
dry with materialThe combined organic layers were dried over Na2SO4
concentrationconcentrated
customThe crude oil was purified by column chromatography (SiO2, 20→100% EtOAc in Hexanes)

Sources & evidence

ORD record: ord-f20f01b499404d73bb549707572d0e8e
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09156823B2

Reaction notes

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