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

HRID 658134Notes

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]>C1COCC1>[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 eq.) and methyl {[(tert-butoxy)carbonyl]amino}-(dimethoxyphosphoryl)acetate (101.5 g, 0.341 mol, 1.0 eq.) are dissolved in THF (800 ml) and cooled to −70° C. At −70° C., TMG (78.7 g, 0.683 mmol, 6.95 ml, 2.0 eq.) is slowly added dropwise and the mixture is then stirred at −70° C. for 4 h and subsequently at RT for 4 days. The reaction mixture is concentrated and then extracted by shaking with ethyl acetate (twice 500 ml) and water, and the combined org. phases are washed with a sat. 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

additionAt −70° C., TMG (78.7 g, 0.683 mmol, 6.95 ml, 2.0 eq.) is slowly added dropwise
concentrationThe reaction mixture is concentrated
extractionextracted
stirringby shaking with ethyl acetate (twice 500 ml) and water
washphases are washed with a sat. sodium chloride solution (100 ml)
dry with materialdried over sodium sulfate
concentrationAfter concentration the crude product
customis chromatographed (1.5 kg of silica gel, eluent: cyclohexane/ethyl acetate 5:1)

Sources & evidence

ORD record: ord-aae22c08ce45473791dac7f143857499
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08076285B2

Reaction notes

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