Pivalaldehyde → Methyl (Z)-2-[(tert-butoxycarbonyl)amino]-4,4-dimethylpent-2-enoate

HRID 2237366Notes

Reaction equation

[CH:1](=O)[C:2]([CH3:5])([CH3:4])[CH3:3].[C:7]([O:11][C:12]([NH:14][CH:15](P(OC)(OC)=O)[C:16]([O:18][CH3:19])=[O:17])=[O:13])([CH3:10])([CH3:9])[CH3:8]>O1CCCC1>[C:7]([O:11][C:12]([NH:14]/[C:15](=[CH:1]\[C:2]([CH3:5])([CH3:4])[CH3:3])/[C:16]([O:18][CH3:19])=[O:17])=[O:13])([CH3:10])([CH3:9])[CH3:8]

Participants

Conditions

Temperature: -70 °C

Procedure

Pivalaldehyde (303.2 g, 3.41 mol, 10 equivalents) and methyl {[tert-butoxycarbonyl]amino}-(dimethoxyphosphoryl)acetate (101.5 g, 0.341 mol, 1.0 equivalent) are dissolved in tetrahydrofuran (800 ml) and cooled to −70° C. At −70° C., N,N,N,N-tetramethylguanidine (78.7 g, 0.683 mmol, 6.95 ml, 2.0 equivalents) is slowly added dropwise and the mixture is then stirred at −70° C. for 4 h, subsequently, the mixture is stirred at RT for 4 days. The reaction mixture is concentrated, then extracted with ethyl acetate (2×500 ml) against water, and the combined organic phases are washed with a saturated sodium chloride solution (100 ml) and dried over sodium sulfate. After concentration, the crude product is chromatographed (1.5 kg of silica gel, eluent: cyclohexane/ethyl acetate 5:1). 67 g (76% of theory) of the title compound are obtained.

Workup

stirringsubsequently, the mixture is stirred at RT for 4 days
concentrationThe reaction mixture is concentrated
extractionextracted with ethyl acetate (2×500 ml) against water
washthe combined organic phases are washed with a saturated sodium chloride solution (100 ml)
dry with materialdried over sodium sulfate
concentrationAfter concentration
customthe crude product is chromatographed (1.5 kg of silica gel, eluent: cyclohexane/ethyl acetate 5:1)

Sources & evidence

ORD record: ord-467591a68e0f4a928f6de8631462fae5
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07718611B2

Reaction notes

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